NPASS Compound

Natural Product: NPC12305

Natural Product ID	NPC12305
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Gyrophoric Acid
IUPAC Name	4-[4-(2,4-dihydroxy-6-methylbenzoyl)oxy-2-hydroxy-6-methylbenzoyl]oxy-2-hydroxy-6-methylbenzoic acid
Synonyms	Gyrophoric Acid
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL470648
PubChem CID	135728
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0001645] Depsides and depsidones

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 54 56 0 0 0 0 0 0 0 0999 V2000 9.9068 -0.9961 -0.0843 O 0 0 0 0 0 0 0 0 0 0 0 0 8.5352 -0.7769 -0.0145 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0745 0.5148 0.1021 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7235 0.8086 0.1769 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2867 2.2173 0.3015 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7872 -0.2310 0.1337 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2565 -1.5306 0.0161 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6128 -1.7938 -0.0565 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3540 -2.6068 -0.0312 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3633 0.0609 0.2113 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9529 1.2392 0.3174 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4296 -0.9598 0.1694 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0689 -0.7532 0.2380 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4156 -0.7369 1.4482 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0304 -0.5265 1.5171 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6708 -0.5085 2.8068 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6706 -0.3347 0.3410 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0325 -0.3479 -0.8778 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3420 -0.5600 -0.8992 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7776 -0.1515 -2.0210 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1303 -0.1095 0.3642 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7904 -0.0819 1.4282 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8395 0.0837 -0.8117 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2102 0.2989 -0.8435 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1336 -0.7271 -0.9414 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4954 -0.4913 -0.9715 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4425 -1.6127 -1.0765 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9626 0.8114 -0.9021 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0468 1.8474 -0.8038 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6924 1.6020 -0.7745 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5250 3.1507 -0.7346 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.3904 1.1167 -0.9299 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0832 1.1880 0.1185 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.0443 1.3429 -2.1348 O 0 0 0 0 0 0 0 0 0 0 0 0 10.5156 -0.3980 0.4352 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7806 1.3459 0.1383 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1889 2.8595 0.2855 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6668 2.5589 -0.5524 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7651 2.3421 1.2866 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9844 -2.8110 -0.1487 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8371 -2.9053 0.7878 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9738 -0.8881 2.3613 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1262 0.4916 2.9601 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0930 -0.6644 3.6245 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4304 -1.3336 2.8526 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8286 -0.5681 -1.8569 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0069 -0.9743 -2.5690 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7696 -1.7419 -0.9955 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2562 -2.1692 -2.0304 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4845 -1.2272 -1.0892 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3286 -2.3638 -0.2568 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0147 2.4348 -0.6974 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5272 3.6863 0.1304 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.8919 1.8801 -2.2198 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 1 0 4 6 2 0 6 7 1 0 7 8 2 0 7 9 1 0 6 10 1 0 10 11 2 0 10 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 15 17 2 0 17 18 1 0 18 19 2 0 18 20 1 0 17 21 1 0 21 22 2 0 21 23 1 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 1 0 26 28 2 0 28 29 1 0 29 30 2 0 29 31 1 0 28 32 1 0 32 33 2 0 32 34 1 0 8 2 1 0 19 13 1 0 30 24 1 0 1 35 1 0 3 36 1 0 5 37 1 0 5 38 1 0 5 39 1 0 8 40 1 0 9 41 1 0 14 42 1 0 16 43 1 0 16 44 1 0 16 45 1 0 19 46 1 0 20 47 1 0 25 48 1 0 27 49 1 0 27 50 1 0 27 51 1 0 30 52 1 0 31 53 1 0 34 54 1 0 M END

Standard InCHIKey	ATQPZSQVWCPVGV-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C24H20O10/c1-10-4-13(25)7-16(26)20(10)23(31)34-15-6-12(3)21(18(28)9-15)24(32)33-14-5-11(2)19(22(29)30)17(27)8-14/h4-9,25-28H,1-3H3,(H,29,30)
SMILES	Oc1cc(C)c(c(c1)O)C(=O)Oc1cc(C)c(c(c1)O)C(=O)Oc1cc(C)c(c(c1)O)C(=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	468.11	Volume:	454.255 ? Van der Waals volume.
Dense:	1.03	LogP:	4.278 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.555 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.424 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	21.0
TPSA:	170.82 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	5.0	Rings:	3.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.275	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.787	Fsp³:	0.125
MCE-18:	24.0 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.648	Fluc inhibitor:	0.913 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.13 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.55 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.596	Promiscuous compounds:	0.441

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.647	MDCK Permeability:	-4.915
Pgp-inhibitor:	0.001	Pgp-substrate:	0.019
PAMPA:	0.953 ? 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):	0.011
20% Bioavailability (F20%):	0.164	30% Bioavailability (F30%):	0.296
50% Bioavailability (F50%):	0.899

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.965
Plasma Protein Binding (PPB):	97.475%	Volume Distribution (VD):	-0.821
Fu:	2.017% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.861
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.085
BSEP inhibitor:	0.048

ADMET: Metabolism

CYP1A2-inhibitor:	0.06	CYP1A2-substrate:	0.145
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.645
CYP2C9-inhibitor:	0.973	CYP2C9-substrate:	0.055
CYP2D6-inhibitor:	0.588	CYP2D6-substrate:	0.816
CYP3A4-inhibitor:	0.003	CYP3A4-substrate:	0.002
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.999 ? 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):

0.519

Half-life (T1/2):

1.838

ADMET: Toxicity

hERG Blockers:	0.018	hERG Blockers (10um):	0.199
Human Hepatotoxicity (H-HT):	0.189	Drug-induced Liver Injury (DILI):	0.855
AMES Toxicity:	0.224	Rat Oral Acute Toxicity:	0.151
Maximum Recommended Daily Dose:	0.249	Skin Sensitization:	0.834
Carcinogencity:	0.177	Eye Corrosion:	0.01
Eye Irritation:	0.995	Respiratory Toxicity:	0.932
Drug-induced Neurotoxicity:	0.047	Ototoxicity:	0.307
Hematotoxicity:	0.038	Drug-induced Nephrotoxicity:	0.314
Genotoxicity:	0.538	RPMI-8226 Immunitoxicity:	0.052
A549 Cytotoxicity:	0.406	Hek293 Cytotoxicity:	0.359
BCF:	1.05 ? 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:	3.946 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.698 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.262 ? 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
NPO22322	Parmotrema tinctorium	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11076561]
NPO28836	Gypsophila pacifica	Species	Caryophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12127	Parmelia saxatilis	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12127	Parmelia saxatilis	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28836	Gypsophila pacifica	Species	Caryophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12127	Parmelia saxatilis	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28836	Gypsophila pacifica	Species	Caryophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12127	Parmelia saxatilis	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO28836	Gypsophila pacifica	Species	Caryophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12127	Parmelia saxatilis	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22322	Parmotrema tinctorium	Species	Parmeliaceae	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
Potency	7
IC50	9
Activity	18
GI50	55

Activity Type	# Activity
Individual protein	7
Cell line	58
Organism	4
Others	20

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT198	Individual protein	Vitamin D receptor	Homo sapiens	Potency	n.a.	79432.8	nM	PubChem BioAssay data set
NPT9	Individual protein	DNA polymerase eta	Homo sapiens	Potency	n.a.	44668.4	nM	PubChem BioAssay data set
NPT831	Individual protein	Serine/threonine-protein kinase PLK1	Homo sapiens	Potency	n.a.	29934.9	nM	PubChem BioAssay data set
NPT446	Individual protein	Rap guanine nucleotide exchange factor 3	Homo sapiens	Potency	n.a.	56234.1	nM	PubChem BioAssay data set
NPT8	Individual protein	DNA polymerase iota	Homo sapiens	Potency	n.a.	1000.0	nM	PubChem BioAssay data set
NPT755	Individual protein	Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1	Homo sapiens	Potency	n.a.	28183.8	nM	PubChem BioAssay data set
NPT535	Individual protein	Parathyroid hormone receptor	Homo sapiens	Potency	n.a.	6309.6	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1195	Cell line	PMNL	n.a.	IC50	>	60000.0	nM	PMID[10395494]
NPT941	Cell line	HaCaT	Homo sapiens	IC50	=	1700.0	nM	PMID[10395495]
NPT941	Cell line	HaCaT	Homo sapiens	Activity	=	138.0	mU	PMID[10395495]
NPT368	Cell line	SN12C	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT370	Cell line	NCI-H23	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT371	Cell line	UO-31	Homo sapiens	GI50	n.a.	76383.58	nM	PubChem BioAssay data set
NPT369	Cell line	ACHN	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT116	Cell line	HL-60	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT372	Cell line	HOP-92	Homo sapiens	GI50	n.a.	69502.43	nM	PubChem BioAssay data set
NPT374	Cell line	SF-539	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT373	Cell line	SK-MEL-5	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT375	Cell line	Malme-3M	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT111	Cell line	K562	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT376	Cell line	A498	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT377	Cell line	OVCAR-3	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT379	Cell line	HOP-62	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT112	Cell line	MOLT-4	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT380	Cell line	U-251	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT381	Cell line	OVCAR-8	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT382	Cell line	OVCAR-5	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT572	Cell line	DMS-273	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT383	Cell line	SNB-19	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT384	Cell line	TK-10	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT573	Cell line	M19-MEL	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT323	Cell line	SW-620	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT455	Cell line	NCI-H522	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT387	Cell line	M14	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT574	Cell line	XF498	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT386	Cell line	KM12	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT388	Cell line	NCI-H322M	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT389	Cell line	RPMI-8226	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT456	Cell line	OVCAR-4	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT390	Cell line	LOX IMVI	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT147	Cell line	SK-MEL-2	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT575	Cell line	KM-20L2	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT81	Cell line	A549	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT391	Cell line	HCC 2998	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT392	Cell line	SNB-75	Homo sapiens	GI50	n.a.	91622.05	nM	PubChem BioAssay data set
NPT395	Cell line	SF-268	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT394	Cell line	EKVX	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT731	Cell line	LXFL 529	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT576	Cell line	DMS-114	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT146	Cell line	SK-OV-3	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT397	Cell line	NCI-H460	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT398	Cell line	UACC-62	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT308	Cell line	CAKI-1	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT399	Cell line	SF-295	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT577	Cell line	RXF 631	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT458	Cell line	IGROV-1	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT578	Cell line	SNB-78	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT401	Cell line	786-0	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT579	Cell line	DLD-1	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT403	Cell line	UACC-257	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT404	Cell line	CCRF-CEM	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT139	Cell line	HT-29	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT170	Cell line	SK-MEL-28	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT406	Cell line	RXF 393	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT407	Cell line	COLO 205	Homo sapiens	GI50	n.a.	100000.0	nM	PubChem BioAssay data set
NPT965	Organism	Amaranthus hypochondriacus	Amaranthus hypochondriacus	IC50	=	200000.0	nM	PMID[11076561]
NPT117	Organism	Echinochloa crus-galli	Echinochloa crus-galli	IC50	=	200000.0	nM	PMID[11076561]
NPT1	Others	Radical scavenging activity	n.a.	Activity	=	3.63	/M/s	PMID[10395494]
NPT2	Others	Unspecified	n.a.	Activity	=	72.1	n.a.	PMID[11076561]
NPT2	Others	Unspecified	n.a.	Activity	=	49.7	n.a.	PMID[11076561]
NPT2	Others	Unspecified	n.a.	Activity	=	31.3	n.a.	PMID[11076561]
NPT2	Others	Unspecified	n.a.	Activity	=	16.8	n.a.	PMID[11076561]
NPT2	Others	Unspecified	n.a.	Activity	=	4.1	n.a.	PMID[11076561]
NPT2	Others	Unspecified	n.a.	Activity	=	93.4	n.a.	PMID[11076561]
NPT2	Others	Unspecified	n.a.	Activity	=	79.9	n.a.	PMID[11076561]
NPT2	Others	Unspecified	n.a.	Activity	=	62.5	n.a.	PMID[11076561]
NPT2	Others	Unspecified	n.a.	Activity	=	41.0	n.a.	PMID[11076561]
NPT2	Others	Unspecified	n.a.	Activity	=	84.3	n.a.	PMID[11076561]
NPT2	Others	Unspecified	n.a.	Activity	=	58.5	n.a.	PMID[11076561]
NPT2	Others	Unspecified	n.a.	Activity	=	40.3	n.a.	PMID[11076561]
NPT2	Others	Unspecified	n.a.	Activity	=	33.8	n.a.	PMID[11076561]
NPT2	Others	Unspecified	n.a.	Activity	=	29.9	n.a.	PMID[11076561]
NPT2	Others	Unspecified	n.a.	Activity	=	17.9	n.a.	PMID[11076561]
NPT2	Others	Unspecified	n.a.	IC50	=	87100.0	nM	PMID[11076561]
NPT2	Others	Unspecified	n.a.	IC50	=	59700.0	nM	PMID[11076561]
NPT2	Others	Unspecified	n.a.	IC50	>	200000.0	nM	PMID[10395494]
NPT2	Others	Unspecified	n.a.	Activity	=	0.12	umol	PMID[10395494]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

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 NPC12305 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	25159
0.1-0.2	22518
0.2-0.3	2042
0.3-0.4	113
0.4-0.5	12
0.5-0.6	10
0.6-0.7	3
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9375	High Similarity	NPC105648
0.6207	Remote Similarity	NPC95123
0.6038	Remote Similarity	NPC220106
0.6032	Remote Similarity	NPC602325
0.5909	Remote Similarity	NPC134621
0.5758	Remote Similarity	NPC146211
0.5672	Remote Similarity	NPC606753
0.5556	Remote Similarity	NPC601451
0.5507	Remote Similarity	NPC604559
0.5493	Remote Similarity	NPC309979
0.549	Remote Similarity	NPC182496
0.5417	Remote Similarity	NPC307780
0.5152	Remote Similarity	NPC66404
0.5067	Remote Similarity	NPC6923

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC12305 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4078
0.1-0.2	4907
0.2-0.3	162
0.3-0.4	3
0.4-0.5	0
0.5-0.6	0
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	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

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