NPASS Compound

Natural Product: NPC299590

Natural Product ID	NPC299590
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Triptolide
IUPAC Name	n.a.
Synonyms	Triptolide
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL463763
PubChem CID	107985
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001729] Oxepanes

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 50 56 0 0 0 0 0 0 0 0999 V2000 4.9349 0.1332 -0.9927 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2439 0.1049 0.3512 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6639 1.3427 1.1094 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7683 -0.0515 0.2375 C 0 0 2 0 0 0 0 0 0 0 0 0 1.9325 -0.1017 1.3500 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5963 -0.7585 1.2890 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0110 -0.9749 -0.0148 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4591 -0.8345 -0.2115 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.9223 -1.2582 -1.5857 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2229 -1.6818 0.7974 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6952 -1.5187 0.6639 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1038 -0.1678 0.1790 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2621 0.8041 -0.0861 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0003 2.0062 -0.5451 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3445 1.6398 -0.5208 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4278 0.3301 -0.0861 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5508 -0.2628 0.0308 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8103 0.6042 0.0881 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9969 1.5949 -0.6470 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2966 1.1230 -1.1859 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7215 -0.1902 -1.0717 C 0 0 1 0 0 0 0 0 0 0 0 0 2.1712 -0.5671 -1.0543 C 0 0 2 0 0 0 0 0 0 0 0 0 2.2609 -1.9771 -1.0772 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0995 0.1462 -2.2553 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5781 -2.0409 0.6140 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0883 1.1658 0.7278 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4543 0.8447 -1.6824 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0593 -0.8841 -1.4170 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9832 0.5242 -0.8396 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6453 -0.7618 0.9333 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6937 1.1758 1.4873 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9640 1.5502 1.9434 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7023 2.1978 0.4142 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3649 -0.0743 2.3934 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0691 -0.6824 2.1642 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1463 -1.8726 -2.1186 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1988 -0.3575 -2.1784 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8307 -1.8977 -1.5488 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9291 -1.4559 1.8401 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9827 -2.7627 0.6158 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1659 -2.3134 0.0188 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1711 -1.6459 1.6603 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8230 2.8667 0.1482 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7284 2.2618 -1.5950 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6082 0.7414 1.1911 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8141 2.5055 -0.0052 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6238 1.9929 -1.4970 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0049 1.9488 -1.4715 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7241 -0.2121 -1.9504 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9247 -2.2988 -0.4091 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 4 2 1 1 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 6 8 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 13 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 21 24 1 6 7 25 1 6 5 26 1 0 22 4 1 0 26 4 1 0 25 6 1 0 21 7 1 0 18 8 1 0 24 20 1 0 16 12 1 0 1 27 1 0 1 28 1 0 1 29 1 0 2 30 1 0 3 31 1 0 3 32 1 0 3 33 1 0 5 34 1 1 6 35 1 1 9 36 1 0 9 37 1 0 9 38 1 0 10 39 1 0 10 40 1 0 11 41 1 0 11 42 1 0 14 43 1 0 14 44 1 0 18 45 1 1 19 46 1 0 19 47 1 0 20 48 1 6 22 49 1 6 23 50 1 0 M END

Standard InCHIKey	DFBIRQPKNDILPW-CIVMWXNOSA-N
Standard InCHI	InChI=1S/C20H24O6/c1-8(2)18-13(25-18)14-20(26-14)17(3)5-4-9-10(7-23-15(9)21)11(17)6-12-19(20,24-12)16(18)22/h8,11-14,16,22H,4-7H2,1-3H3/t11-,12-,13-,14-,16+,17-,18-,19+,20+/m0/s1
SMILES	CC(C)[C@]12[C@H]([C@H]3[C@]4([C@@]5(C)CCC6=C(COC6=O)[C@@H]5C[C@H]5[C@]4([C@@H]1O)O5)O3)O2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	360.16	Volume:	342.049 ? Van der Waals volume.
Dense:	1.053	LogP:	1.717 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.922 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.949 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	27.0
TPSA:	84.12 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	1.0	Rings:	7.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.557	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.156	Fsp³:	0.85
MCE-18:	155.514 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.411	Fluc inhibitor:	0.006 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.035 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.158	Promiscuous compounds:	0.21

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.121	MDCK Permeability:	-4.768
Pgp-inhibitor:	0.769	Pgp-substrate:	0.168
PAMPA:	0.151 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.005
20% Bioavailability (F20%):	0.262	30% Bioavailability (F30%):	0.308
50% Bioavailability (F50%):	0.782

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.128	MRP1:	0.955
Plasma Protein Binding (PPB):	79.925%	Volume Distribution (VD):	0.134
Fu:	14.515% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.895	BCRP inhibitor:	0.023
BSEP inhibitor:	0.967

ADMET: Metabolism

CYP1A2-inhibitor:	0.107	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.122	CYP2C19-substrate:	0.005
CYP2C9-inhibitor:	0.046	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.01
CYP3A4-inhibitor:	0.407	CYP3A4-substrate:	0.17
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.61
HLM stability:	0.813 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

8.189

Half-life (T1/2):

1.817

ADMET: Toxicity

hERG Blockers:	0.025	hERG Blockers (10um):	0.226
Human Hepatotoxicity (H-HT):	0.486	Drug-induced Liver Injury (DILI):	0.569
AMES Toxicity:	0.99	Rat Oral Acute Toxicity:	0.899
Maximum Recommended Daily Dose:	0.863	Skin Sensitization:	1.0
Carcinogencity:	0.97	Eye Corrosion:	0.001
Eye Irritation:	0.553	Respiratory Toxicity:	0.347
Drug-induced Neurotoxicity:	0.772	Ototoxicity:	0.575
Hematotoxicity:	0.629	Drug-induced Nephrotoxicity:	0.894
Genotoxicity:	0.868	RPMI-8226 Immunitoxicity:	0.545
A549 Cytotoxicity:	0.48	Hek293 Cytotoxicity:	0.891
BCF:	1.907 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	4.107 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.464 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.023 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	DOI[10.1016/S0040-4039(99)00339-1]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[10746886]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10757718]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	root bark	Kunming, Yunnan, China	n.a.	PMID[10757718]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[10757718]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[22256754]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22256754]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[23252270]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[2534610]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Europe PMC[535601]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8328267]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	Database[Article]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	leaf	n.a.	Database[Article]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[Article]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[Phytochemistry, 2000, 53, 715-722.]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	root bark	Kunming, Yunnan, China	n.a.	Database[Title]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[Title]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	root bark	n.a.	n.a.	Database[Title]
NPO1152	Tripterygium hypoglaucum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	91
Potency	20
Activity	32
Inhibition	15
ED50	1
EC50	4
GI50	60
ILS	2
TGI	2
IC50 relative	1

Activity Type	# Activity
Individual protein	19
Cell line	161
Protein-protein interaction	1
Organism	14
Unchecked	3
Nucleic acid	2
Single protein	2
Non-molecular	12
Others	14

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT31	Individual protein	Cyclooxygenase-2	Homo sapiens	IC50	=	40.0	nM	PMID[16038536]
NPT1583	Individual protein	Heat shock factor protein 1	Homo sapiens	Activity	=	45.0	%	PMID[26164188]
NPT1583	Individual protein	Heat shock factor protein 1	Homo sapiens	Activity	=	35.0	%	PMID[26164188]
NPT1583	Individual protein	Heat shock factor protein 1	Homo sapiens	Activity	=	40.0	%	PMID[26164188]
NPT483	Individual protein	Prelamin-A/C	Homo sapiens	Potency	=	89.1	nM	PubChem BioAssay data set
NPT537	Individual protein	Ras-related protein Rab-9A	Homo sapiens	Potency	=	1000.0	nM	PubChem BioAssay data set
NPT531	Individual protein	Nuclear receptor ROR-gamma	Mus musculus	Potency	=	398.1	nM	PubChem BioAssay data set
NPT531	Individual protein	Nuclear receptor ROR-gamma	Mus musculus	Potency	=	316.2	nM	PubChem BioAssay data set
NPT533	Protein-protein interaction	Runt-related transcription factor 1/Core-binding factor subunit beta	Homo sapiens	Potency	n.a.	28183.8	nM	PubChem BioAssay data set
NPT538	Individual protein	Niemann-Pick C1 protein	Homo sapiens	Potency	=	89.1	nM	PubChem BioAssay data set
NPT20556	Single protein	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	6.6	%	DOI[10.6019/CHEMBL4495564]
NPT20556	Single protein	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	-6.471	%	DOI[10.6019/CHEMBL4495564]
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	-0.71	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	0.43	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT4559	Individual protein	Proteinase-activated receptor 2	Homo sapiens	IC50	=	23.0	nM	PMID[23895492]
NPT4559	Individual protein	Proteinase-activated receptor 2	Homo sapiens	IC50	=	14.0	nM	PMID[23895492]
NPT536	Nucleic acid	microRNA 21	Homo sapiens	Potency	=	18.5	nM	PubChem BioAssay data set
NPT53	Individual protein	4'-phosphopantetheinyl transferase ffp	Bacillus subtilis	Potency	=	14125.4	nM	PubChem BioAssay data set
NPT5825	Individual protein	dCTP pyrophosphatase 1	Homo sapiens	IC50	=	30900.0	nM	PMID[26771665]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT81	Cell line	A549	Homo sapiens	IC50	=	0.0013	ug.mL-1	PMID[18321701]
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	0.0001	ug.mL-1	PMID[18321701]
NPT91	Cell line	KB	Homo sapiens	ED50	=	2.6	ug ml-1	PMID[7130986]
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	20.0	nM	PMID[24378709]
NPT784	Cell line	MDA-MB-468	Homo sapiens	IC50	=	10.0	nM	PMID[19637874]
NPT146	Cell line	SK-OV-3	Homo sapiens	IC50	=	9.0	nM	PMID[19637874]
NPT112	Cell line	MOLT-4	Homo sapiens	IC50	=	17.0	nM	PMID[19637874]
NPT111	Cell line	K562	Homo sapiens	IC50	=	50.0	nM	PMID[19637874]
NPT81	Cell line	A549	Homo sapiens	IC50	=	59.0	nM	PMID[19637874]
NPT515	Cell line	SGC-7901	Homo sapiens	IC50	=	15.0	nM	PMID[19637874]
NPT1179	Cell line	MKN-28	Homo sapiens	IC50	=	200.0	nM	PMID[19637874]
NPT393	Cell line	HCT-116	Homo sapiens	IC50	=	10.0	nM	PMID[19637874]
NPT148	Cell line	HCT-15	Homo sapiens	IC50	=	29.0	nM	PMID[19637874]
NPT659	Cell line	SMMC-7721	Homo sapiens	IC50	=	18.0	nM	PMID[19637874]
NPT181	Cell line	Bel-7402	Homo sapiens	IC50	=	20.0	nM	PMID[19637874]
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	=	24.0	nM	PMID[19637874]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	19.0	nM	PMID[19637874]
NPT146	Cell line	SK-OV-3	Homo sapiens	IC50	=	10.0	nM	PMID[19637874]
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	43.0	nM	PMID[19637874]
NPT90	Cell line	DU-145	Homo sapiens	IC50	=	24.0	nM	PMID[19637874]
NPT91	Cell line	KB	Homo sapiens	IC50	=	43.0	nM	PMID[19637874]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	47.0	nM	PMID[19637874]
NPT380	Cell line	U-251	Homo sapiens	IC50	=	49.0	nM	PMID[19637874]
NPT1893	Cell line	MEF	Mus musculus	IC50	=	9200.0	nM	PMID[20149665]
NPT146	Cell line	SK-OV-3	Homo sapiens	IC50	=	6.0	nM	PMID[24378709]
NPT81	Cell line	A549	Homo sapiens	IC50	=	19.0	nM	PMID[21470864]
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	2.1	nM	PMID[21470864]
NPT1160	Cell line	BJ	Homo sapiens	EC50	<	104.0	nM	PubChem BioAssay data set
NPT368	Cell line	SN12C	Homo sapiens	GI50	n.a.	8.61	nM	PubChem BioAssay data set
NPT367	Cell line	MDA-N	Homo sapiens	GI50	n.a.	7.586	nM	PubChem BioAssay data set
NPT370	Cell line	NCI-H23	Homo sapiens	GI50	n.a.	3.221	nM	PubChem BioAssay data set
NPT369	Cell line	ACHN	Homo sapiens	GI50	n.a.	6.792	nM	PubChem BioAssay data set
NPT371	Cell line	UO-31	Homo sapiens	GI50	n.a.	12.39	nM	PubChem BioAssay data set
NPT372	Cell line	HOP-92	Homo sapiens	GI50	n.a.	23.01	nM	PubChem BioAssay data set
NPT116	Cell line	HL-60	Homo sapiens	GI50	n.a.	6.668	nM	PubChem BioAssay data set
NPT374	Cell line	SF-539	Homo sapiens	GI50	n.a.	7.447	nM	PubChem BioAssay data set
NPT90	Cell line	DU-145	Homo sapiens	GI50	n.a.	24.38	nM	PubChem BioAssay data set
NPT373	Cell line	SK-MEL-5	Homo sapiens	GI50	n.a.	6.966	nM	PubChem BioAssay data set
NPT375	Cell line	Malme-3M	Homo sapiens	GI50	n.a.	11.19	nM	PubChem BioAssay data set
NPT111	Cell line	K562	Homo sapiens	GI50	n.a.	17.02	nM	PubChem BioAssay data set
NPT377	Cell line	OVCAR-3	Homo sapiens	GI50	n.a.	5.861	nM	PubChem BioAssay data set
NPT376	Cell line	A498	Homo sapiens	GI50	n.a.	18.03	nM	PubChem BioAssay data set
NPT112	Cell line	MOLT-4	Homo sapiens	GI50	n.a.	7.638	nM	PubChem BioAssay data set
NPT379	Cell line	HOP-62	Homo sapiens	GI50	n.a.	7.015	nM	PubChem BioAssay data set
NPT378	Cell line	NCI/ADR-RES	Homo sapiens	GI50	n.a.	26.06	nM	PubChem BioAssay data set
NPT380	Cell line	U-251	Homo sapiens	GI50	n.a.	60.95	nM	PubChem BioAssay data set
NPT381	Cell line	OVCAR-8	Homo sapiens	GI50	n.a.	20.32	nM	PubChem BioAssay data set
NPT382	Cell line	OVCAR-5	Homo sapiens	GI50	n.a.	21.38	nM	PubChem BioAssay data set
NPT383	Cell line	SNB-19	Homo sapiens	GI50	n.a.	103.51	nM	PubChem BioAssay data set
NPT385	Cell line	SR	Homo sapiens	GI50	n.a.	17.34	nM	PubChem BioAssay data set
NPT82	Cell line	MDA-MB-231	Homo sapiens	GI50	n.a.	14.49	nM	PubChem BioAssay data set
NPT384	Cell line	TK-10	Homo sapiens	GI50	n.a.	13.96	nM	PubChem BioAssay data set
NPT323	Cell line	SW-620	Homo sapiens	GI50	n.a.	14.09	nM	PubChem BioAssay data set
NPT455	Cell line	NCI-H522	Homo sapiens	GI50	n.a.	8.81	nM	PubChem BioAssay data set
NPT387	Cell line	M14	Homo sapiens	GI50	n.a.	13.55	nM	PubChem BioAssay data set
NPT386	Cell line	KM12	Homo sapiens	GI50	n.a.	27.35	nM	PubChem BioAssay data set
NPT388	Cell line	NCI-H322M	Homo sapiens	GI50	n.a.	11.35	nM	PubChem BioAssay data set
NPT389	Cell line	RPMI-8226	Homo sapiens	GI50	n.a.	4.699	nM	PubChem BioAssay data set
NPT456	Cell line	OVCAR-4	Homo sapiens	GI50	n.a.	7.925	nM	PubChem BioAssay data set
NPT390	Cell line	LOX IMVI	Homo sapiens	GI50	n.a.	5.14	nM	PubChem BioAssay data set
NPT457	Cell line	BT-549	Homo sapiens	GI50	n.a.	10.86	nM	PubChem BioAssay data set
NPT147	Cell line	SK-MEL-2	Homo sapiens	GI50	n.a.	6.427	nM	PubChem BioAssay data set
NPT81	Cell line	A549	Homo sapiens	GI50	n.a.	20.14	nM	PubChem BioAssay data set
NPT392	Cell line	SNB-75	Homo sapiens	GI50	n.a.	10.09	nM	PubChem BioAssay data set
NPT391	Cell line	HCC 2998	Homo sapiens	GI50	n.a.	18.28	nM	PubChem BioAssay data set
NPT148	Cell line	HCT-15	Homo sapiens	GI50	n.a.	13.96	nM	PubChem BioAssay data set
NPT393	Cell line	HCT-116	Homo sapiens	GI50	n.a.	2.582	nM	PubChem BioAssay data set
NPT395	Cell line	SF-268	Homo sapiens	GI50	n.a.	24.89	nM	PubChem BioAssay data set
NPT83	Cell line	MCF7	Homo sapiens	GI50	n.a.	4.266	nM	PubChem BioAssay data set
NPT394	Cell line	EKVX	Homo sapiens	GI50	n.a.	20.99	nM	PubChem BioAssay data set
NPT306	Cell line	PC-3	Homo sapiens	GI50	n.a.	18.11	nM	PubChem BioAssay data set
NPT396	Cell line	T47D	Homo sapiens	GI50	n.a.	18.71	nM	PubChem BioAssay data set
NPT146	Cell line	SK-OV-3	Homo sapiens	GI50	n.a.	47.42	nM	PubChem BioAssay data set
NPT398	Cell line	UACC-62	Homo sapiens	GI50	n.a.	4.207	nM	PubChem BioAssay data set
NPT397	Cell line	NCI-H460	Homo sapiens	GI50	n.a.	5.272	nM	PubChem BioAssay data set
NPT400	Cell line	MDA-MB-435	Homo sapiens	GI50	n.a.	6.934	nM	PubChem BioAssay data set
NPT308	Cell line	CAKI-1	Homo sapiens	GI50	n.a.	6.026	nM	PubChem BioAssay data set
NPT458	Cell line	IGROV-1	Homo sapiens	GI50	n.a.	7.129	nM	PubChem BioAssay data set
NPT399	Cell line	SF-295	Homo sapiens	GI50	n.a.	27.86	nM	PubChem BioAssay data set
NPT402	Cell line	Hs-578T	Homo sapiens	GI50	n.a.	14.96	nM	PubChem BioAssay data set
NPT401	Cell line	786-0	Homo sapiens	GI50	n.a.	16.94	nM	PubChem BioAssay data set
NPT404	Cell line	CCRF-CEM	Homo sapiens	GI50	n.a.	10.96	nM	PubChem BioAssay data set
NPT403	Cell line	UACC-257	Homo sapiens	GI50	n.a.	12.65	nM	PubChem BioAssay data set
NPT405	Cell line	NCI-H226	Homo sapiens	GI50	n.a.	21.63	nM	PubChem BioAssay data set
NPT139	Cell line	HT-29	Homo sapiens	GI50	n.a.	8.299	nM	PubChem BioAssay data set
NPT170	Cell line	SK-MEL-28	Homo sapiens	GI50	n.a.	6.368	nM	PubChem BioAssay data set
NPT407	Cell line	COLO 205	Homo sapiens	GI50	n.a.	7.762	nM	PubChem BioAssay data set
NPT406	Cell line	RXF 393	Homo sapiens	GI50	n.a.	7.87	nM	PubChem BioAssay data set
NPT380	Cell line	U-251	Homo sapiens	IC50	=	33.0	nM	PMID[25467158]
NPT146	Cell line	SK-OV-3	Homo sapiens	IC50	=	7.2	nM	PMID[28011223]
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	18.3	nM	PMID[28011223]
NPT81	Cell line	A549	Homo sapiens	IC50	=	17.5	nM	PMID[28011223]
NPT81	Cell line	A549	Homo sapiens	IC50	=	30.0	nM	PMID[28814374]
NPT2316	Cell line	CFPAC-1	Homo sapiens	Activity	<	0.4	g	PMID[31784199]
NPT461	Cell line	PANC-1	Homo sapiens	Activity	<	0.4	g	PMID[31784199]
NPT2316	Cell line	CFPAC-1	Homo sapiens	Activity	<	10.0	%	PMID[31784199]
NPT461	Cell line	PANC-1	Homo sapiens	Activity	<	10.0	%	PMID[31784199]
NPT393	Cell line	HCT-116	Homo sapiens	IC50	=	4.7	nM	PMID[31121546]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	87.0	nM	PMID[31121546]
NPT616	Cell line	MDCK	Canis lupus familiaris	IC50	=	1200.0	nM	PMID[31121546]
NPT15	Cell line	Jurkat	Homo sapiens	IC50	=	140.0	nM	PMID[31121546]
NPT886	Cell line	NIH3T3	Mus musculus	IC50	=	50.0	nM	PMID[31121546]
NPT65	Cell line	HepG2	Homo sapiens	IC50	=	43.3	nM	PMID[30613335]
NPT984	Cell line	Hepatocyte	n.a.	IC50	=	37.7	nM	PMID[30613335]
NPT393	Cell line	HCT-116	Homo sapiens	IC50	=	3.0	nM	PMID[32028140]
NPT65	Cell line	HepG2	Homo sapiens	IC50	=	14.0	nM	PMID[32028140]
NPT547	Cell line	BGC-823	Homo sapiens	IC50	=	2.0	nM	PMID[32028140]
NPT1820	Cell line	NCI-H1650	Homo sapiens	IC50	=	15.0	nM	PMID[32028140]
NPT113	Cell line	RAW264.7	Mus musculus	IC50	=	14.0	nM	PMID[32028140]
NPT113	Cell line	RAW264.7	Mus musculus	IC50	=	23.0	nM	PMID[32028140]
NPT461	Cell line	PANC-1	Homo sapiens	IC50	=	200.0	nM	PMID[33289552]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	87.8	%	PMID[35617856]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	3.85	%	PMID[35617856]
NPT2341	Cell line	NCI-H1975	Homo sapiens	IC50	=	19.0	nM	PMID[34700239]
NPT65	Cell line	HepG2	Homo sapiens	IC50	=	33.0	nM	PMID[34700239]
NPT65	Cell line	HepG2	Homo sapiens	Activity	n.a.	n.a.	n.a.	PMID[34700239]
NPT660	Cell line	SW480	Homo sapiens	IC50	=	50.0	nM	PMID[33445154]
NPT1649	Cell line	MV4-11	Homo sapiens	TGI	=	91.54	%	PMID[36115206]
NPT397	Cell line	NCI-H460	Homo sapiens	IC50	=	14.0	nM	PMID[35617856]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	43.0	nM	PMID[34700239]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	56.8	%	PMID[35617856]
NPT941	Cell line	HaCaT	Homo sapiens	IC50	=	27.0	nM	PMID[35617856]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	n.a.	n.a.	n.a.	PMID[35617856]
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	=	51.0	nM	PMID[35617856]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	25.1	%	PMID[35617856]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	5.7	%	PMID[35617856]
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	21.0	nM	PMID[34700239]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	6.84	%	PMID[35617856]
NPT1649	Cell line	MV4-11	Homo sapiens	IC50	=	12.03	nM	PMID[36115206]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	29.5	%	PMID[35617856]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	2.34	%	PMID[35617856]
NPT461	Cell line	PANC-1	Homo sapiens	IC50	=	56.0	nM	PMID[34700239]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	22.0	nM	PMID[34700239]
NPT393	Cell line	HCT-116	Homo sapiens	IC50	=	46.0	nM	PMID[35617856]
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	47.0	nM	PMID[35617856]
NPT65	Cell line	HepG2	Homo sapiens	IC50 relative	<	100.0	nM	ECBD screening data for assay EOS300108
NPT858	Cell line	LNCaP	Homo sapiens	IC50	=	9.7	nM	PMID[35247754]
NPT1970	Cell line	THP-1	Homo sapiens	IC50	=	7.04	nM	PMID[36115206]
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	20.3	nM	PMID[35247754]
NPT2410	Cell line	NCI-H1299	Homo sapiens	IC50	=	49.0	nM	PMID[34700239]
NPT65	Cell line	HepG2	Homo sapiens	IC50	=	468.0	nM	PMID[35476958]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	42.2	%	PMID[35617856]
NPT323	Cell line	SW-620	Homo sapiens	IC50	=	163.0	nM	PMID[35617856]
NPT397	Cell line	NCI-H460	Homo sapiens	TGI	=	28.65	%	PMID[35617856]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	3.17	%	PMID[35617856]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	2.2	%	PMID[35617856]
NPT737	Cell line	HUVEC	Homo sapiens	IC50	=	44.0	nM	PMID[35617856]
NPT2341	Cell line	NCI-H1975	Homo sapiens	IC50	=	2.0	nM	PMID[35617856]
NPT397	Cell line	NCI-H460	Homo sapiens	Activity	=	24.4	%	PMID[35617856]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	90.67	%	DOI[10.21203/rs.3.rs-23951/v1]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	2.1	%	DOI[10.6019/CHEMBL4495565]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	1.32	%	DOI[10.6019/CHEMBL4495565]
NPT28438	Unchecked	Unchecked	n.a.	IC50	>	10000.0	nM	PMID[34700239]
NPT28438	Unchecked	Unchecked	n.a.	Activity	n.a.	n.a.	n.a.	PMID[35617856]
NPT28438	Unchecked	Unchecked	n.a.	IC50	=	30.0	nM	PMID[34700239]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	>	90.0	%	PMID[17360534]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	>	50.0	%	PMID[17360534]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	>	80.0	%	PMID[17360534]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	52.0	nM	PMID[19637874]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	22.0	nM	PMID[19637874]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	28.0	nM	PMID[19637874]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	14.0	nM	PMID[19637874]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	34.0	nM	PMID[20149665]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	32.0	nM	PMID[20149665]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	8.3	nM	PMID[20149665]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	10.3	nM	PMID[20149665]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	20.0	nM	PMID[25467158]
NPT20	Organism	Candida albicans	Candida albicans	Inhibition	=	1.65	%	DOI[10.6019/CHEMBL4513141]
NPT173	Organism	Klebsiella pneumoniae	Klebsiella pneumoniae	Inhibition	=	7.24	%	DOI[10.6019/CHEMBL4513141]
NPT530	Organism	Caenorhabditis elegans	Caenorhabditis elegans	ILS	=	20.0	%	PMID[28814374]
NPT19	Organism	Escherichia coli	Escherichia coli	Inhibition	=	-9.75	%	DOI[10.6019/CHEMBL4513141]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	Inhibition	=	24.45	%	DOI[10.6019/CHEMBL4513141]
NPT21742	Cell line	L02	Homo sapiens	IC50	=	21.0	nM	PMID[34700239]
NPT21742	Cell line	L02	Homo sapiens	IC50	=	16.0	nM	PMID[35617856]
NPT2	Others	Unspecified	n.a.	EC50	<	100.0	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	=	819.9	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	13.2	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	33.5	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	14.8	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	132.1	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	2818.4	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	3.7	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	2.1	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	7.4	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	66.2	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	4.2	nM	PubChem BioAssay data set
NPT747	Organism	Acinetobacter baumannii	Acinetobacter baumannii	Inhibition	=	17.86	%	DOI[10.6019/CHEMBL4513141]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT32	Organism	Mus musculus	Mus musculus	Inhibition	=	19.3	%	PMID[32028140]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Activity	=	100.0	%	PMID[34633803]

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference
n.a.	n.a.	LogP	=	-0.56	n.a.	PMID[35617856]
Rattus norvegicus	n.a.	Tmax	=	0.44	hr	PMID[36115206]
Rattus norvegicus	n.a.	AUC	=	31.86	ng.hr.mL-1	PMID[36115206]
Rattus norvegicus	n.a.	Cmax	=	44.17	nM	PMID[36115206]
Rattus norvegicus	n.a.	Vd/F	=	15352.03	L.kg-1	PMID[36115206]

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC299590 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	19489
0.1-0.2	27973
0.2-0.3	2390
0.3-0.4	3
0.4-0.5	1
0.5-0.6	0
0.6-0.7	1
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.7333	Intermediate Similarity	NPC42658
0.6154	Remote Similarity	NPC33360

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC299590 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6835
0.1-0.2	2270
0.2-0.3	42
0.3-0.4	0
0.4-0.5	0
0.5-0.6	2
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD4061	Phase 3
0.5541	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.5467	Remote Similarity	NPD5955	Clinical (unspecified phase)

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data