NPASS Compound

Natural Product: NPC180079

Natural Product ID	NPC180079
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(3S,5S,8R,9S,10S,13R,14S,17R)-5,14-Dihydroxy-3-[(2R,4S,5R,6R)-5-Hydroxy-4-Methoxy-6-Methyloxan-2-Yl]Oxy-13-Methyl-17-(5-Oxo-2H-Furan-3-Yl)-2,3,4,6,7,8,9,11,12,15,16,17-Dodecahydro-1H-Cyclopenta[A]Phenanthrene-10-Carbaldehyde
IUPAC Name	(3S,5S,8R,9S,10S,13R,14S,17R)-5,14-dihydroxy-3-[(2R,4S,5R,6R)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-13-methyl-17-(5-oxo-2H-furan-3-yl)-2,3,4,6,7,8,9,11,12,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-10-carbaldehyde
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1075788
PubChem CID	441853
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001555] Cardenolides and derivatives [CHEMONTID:0001559] Cardenolide glycosides and derivatives

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 83 88 0 0 0 0 0 0 0 0999 V2000 -7.9820 -0.3679 2.0540 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0343 -0.5889 1.0366 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.0454 0.5227 0.1976 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.6636 1.1129 0.1882 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6826 0.0627 -0.3382 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.4748 0.7100 -0.5185 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4439 0.1253 0.2566 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4323 -0.3817 -0.7587 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6109 0.7878 -1.1737 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3098 1.3095 -0.0682 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3644 1.1408 1.2485 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8953 1.2062 1.1178 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0806 2.2738 2.0406 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0402 -0.0747 2.0125 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1980 -0.8027 1.6734 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2385 0.0413 0.9778 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6226 0.6617 -0.2241 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6693 1.6323 -0.7805 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9618 0.9599 -1.0537 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5291 0.1031 0.0197 C 0 0 1 0 0 0 0 0 0 0 0 0 3.4685 -0.7259 0.6997 C 0 0 1 0 0 0 0 0 0 0 0 0 4.0156 -1.1468 1.9480 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3674 -1.9449 -0.1277 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8814 -2.2871 -0.2130 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4343 -0.9312 -0.5984 C 0 0 2 0 0 0 0 0 0 0 0 0 6.8659 -0.7617 -0.3698 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6805 -1.6052 0.2794 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0344 -1.0835 0.2981 C 0 0 0 0 0 0 0 0 0 0 0 0 10.0229 -1.6777 0.8481 O 0 0 0 0 0 0 0 0 0 0 0 0 9.0070 0.1116 -0.3656 O 0 0 0 0 0 0 0 0 0 0 0 0 7.7256 0.3375 -0.8543 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2871 0.9213 1.0589 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4188 2.7786 -0.3214 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1385 3.3389 -1.2513 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0912 -0.4206 -1.5801 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3304 -1.0476 -1.5176 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.3510 0.0340 -1.2017 C 0 0 1 0 0 0 0 0 0 0 0 0 -8.6332 -0.4704 -1.3158 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5879 -1.6870 -2.8612 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9642 -1.2553 2.7125 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9601 -0.2064 1.5562 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6424 0.5484 2.5946 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7769 1.2883 0.5273 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3075 1.4249 1.1767 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5923 1.9816 -0.5013 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6066 -0.7772 0.3698 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8809 -0.7193 0.8203 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9888 -0.7095 -1.6813 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8863 -1.2570 -0.4185 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2895 1.5803 -1.5352 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0164 0.4737 -2.0451 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2733 1.0357 2.1584 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1985 2.2180 0.8408 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8546 2.4955 2.1026 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8878 -0.8235 1.9588 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0066 0.1745 3.1160 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9864 -1.6618 1.0128 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6830 -1.2191 2.6054 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5301 0.8289 1.7374 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5885 -0.1564 -1.0054 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2598 2.0002 -1.7438 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7406 2.4798 -0.0689 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8971 0.4118 -2.0272 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7170 1.7764 -1.2543 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6065 -2.0209 2.1897 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0850 -1.7836 -1.1810 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8514 -2.7969 0.3363 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0578 -3.0554 -0.9908 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2155 -2.6585 0.7516 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2736 -0.8983 -1.7319 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3730 -2.5431 0.7268 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3201 1.3241 -0.5854 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6907 0.2443 -1.9870 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2236 0.4281 1.2930 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4282 1.9251 0.6707 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6094 0.9850 1.9414 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0064 3.4528 0.3110 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3438 -1.8283 -0.7246 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1844 0.8647 -1.9211 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9755 -0.1870 -2.2170 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1532 -1.1160 -3.6998 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2674 -2.7417 -2.8445 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6851 -1.6930 -3.0227 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 11 13 1 1 11 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 1 21 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 28 30 1 0 30 31 1 0 20 32 1 1 10 33 1 6 33 34 2 0 5 35 1 0 35 36 1 0 36 37 1 0 37 38 1 0 36 39 1 0 37 3 1 0 12 7 1 0 21 16 1 0 31 26 1 0 17 10 1 0 25 20 1 0 1 40 1 0 1 41 1 0 1 42 1 0 3 43 1 1 4 44 1 0 4 45 1 0 5 46 1 1 7 47 1 1 8 48 1 0 8 49 1 0 9 50 1 0 9 51 1 0 12 52 1 0 12 53 1 0 13 54 1 0 14 55 1 0 14 56 1 0 15 57 1 0 15 58 1 0 16 59 1 1 17 60 1 6 18 61 1 0 18 62 1 0 19 63 1 0 19 64 1 0 22 65 1 0 23 66 1 0 23 67 1 0 24 68 1 0 24 69 1 0 25 70 1 6 27 71 1 0 31 72 1 0 31 73 1 0 32 74 1 0 32 75 1 0 32 76 1 0 33 77 1 0 36 78 1 1 37 79 1 6 38 80 1 0 39 81 1 0 39 82 1 0 39 83 1 0 M END

Standard InCHIKey	XQCGNURMLWFQJR-ZNDDOCHDSA-N
Standard InCHI	InChI=1S/C30H44O9/c1-17-26(33)23(36-3)13-25(38-17)39-19-4-9-28(16-31)21-5-8-27(2)20(18-12-24(32)37-15-18)7-11-30(27,35)22(21)6-10-29(28,34)14-19/h12,16-17,19-23,25-26,33-35H,4-11,13-15H2,1-3H3/t17-,19+,20-,21+,22-,23+,25+,26-,27-,28+,29+,30+/m1/s1
SMILES	CO[C@H]1C[C@H](O[C@H]2CC[C@]3([C@](C2)(O)CC[C@@H]2[C@@H]3CC[C@]3([C@]2(O)CC[C@@H]3C2=CC(=O)OC2)C)C=O)O[C@@H]([C@H]1O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	548.3	Volume:	547.3 ? Van der Waals volume.
Dense:	1.002	LogP:	1.182 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.749 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.571 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	33.0
TPSA:	131.75 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	3.0	Rings:	6.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.269	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.331	Fsp³:	0.867
MCE-18:	112.857 ? 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:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.816	Fluc inhibitor:	0.005 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.016 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.002 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.178	Promiscuous compounds:	0.534

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.599	MDCK Permeability:	-5.157
Pgp-inhibitor:	0.001	Pgp-substrate:	0.979
PAMPA:	0.994 ? 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):	0.017
20% Bioavailability (F20%):	0.248	30% Bioavailability (F30%):	0.222
50% Bioavailability (F50%):	0.928

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.067	MRP1:	0.546
Plasma Protein Binding (PPB):	62.953%	Volume Distribution (VD):	-0.091
Fu:	36.578% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.989
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.049
BSEP inhibitor:	0.572

ADMET: Metabolism

CYP1A2-inhibitor:	0.911	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.745	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.011	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.002
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.079
HLM stability:	0.035 ? 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):

5.174

Half-life (T1/2):

3.395

ADMET: Toxicity

hERG Blockers:	0.257	hERG Blockers (10um):	0.793
Human Hepatotoxicity (H-HT):	0.809	Drug-induced Liver Injury (DILI):	0.762
AMES Toxicity:	0.906	Rat Oral Acute Toxicity:	0.995
Maximum Recommended Daily Dose:	1.0	Skin Sensitization:	1.0
Carcinogencity:	0.976	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.995
Drug-induced Neurotoxicity:	0.024	Ototoxicity:	0.646
Hematotoxicity:	0.456	Drug-induced Nephrotoxicity:	0.965
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.849
A549 Cytotoxicity:	0.877	Hek293 Cytotoxicity:	0.992
BCF:	0.584 ? 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:	3.386 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.976 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.326 ? 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
NPO16145	Apocynum venetum	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16145	Apocynum venetum	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO16145	Apocynum venetum	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16145	Apocynum venetum	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO16145	Apocynum venetum	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]

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
GI50	60
IC50	1

Activity Type	# Activity
Cell line	60
Protein complex	1

Molecular-level activity

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

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT368	Cell line	SN12C	Homo sapiens	GI50	n.a.	41.98	nM	PubChem BioAssay data set
NPT367	Cell line	MDA-N	Homo sapiens	GI50	n.a.	136.14	nM	PubChem BioAssay data set
NPT370	Cell line	NCI-H23	Homo sapiens	GI50	n.a.	156.68	nM	PubChem BioAssay data set
NPT371	Cell line	UO-31	Homo sapiens	GI50	n.a.	308.32	nM	PubChem BioAssay data set
NPT369	Cell line	ACHN	Homo sapiens	GI50	n.a.	91.2	nM	PubChem BioAssay data set
NPT116	Cell line	HL-60	Homo sapiens	GI50	n.a.	118.03	nM	PubChem BioAssay data set
NPT372	Cell line	HOP-92	Homo sapiens	GI50	n.a.	341.19	nM	PubChem BioAssay data set
NPT374	Cell line	SF-539	Homo sapiens	GI50	n.a.	80.91	nM	PubChem BioAssay data set
NPT90	Cell line	DU-145	Homo sapiens	GI50	n.a.	114.55	nM	PubChem BioAssay data set
NPT373	Cell line	SK-MEL-5	Homo sapiens	GI50	n.a.	99.31	nM	PubChem BioAssay data set
NPT375	Cell line	Malme-3M	Homo sapiens	GI50	n.a.	225.42	nM	PubChem BioAssay data set
NPT111	Cell line	K562	Homo sapiens	GI50	n.a.	184.08	nM	PubChem BioAssay data set
NPT376	Cell line	A498	Homo sapiens	GI50	n.a.	294.44	nM	PubChem BioAssay data set
NPT377	Cell line	OVCAR-3	Homo sapiens	GI50	n.a.	145.55	nM	PubChem BioAssay data set
NPT379	Cell line	HOP-62	Homo sapiens	GI50	n.a.	113.5	nM	PubChem BioAssay data set
NPT112	Cell line	MOLT-4	Homo sapiens	GI50	n.a.	88.31	nM	PubChem BioAssay data set
NPT378	Cell line	NCI/ADR-RES	Homo sapiens	GI50	n.a.	257.04	nM	PubChem BioAssay data set
NPT380	Cell line	U-251	Homo sapiens	GI50	n.a.	314.05	nM	PubChem BioAssay data set
NPT381	Cell line	OVCAR-8	Homo sapiens	GI50	n.a.	306.9	nM	PubChem BioAssay data set
NPT382	Cell line	OVCAR-5	Homo sapiens	GI50	n.a.	477.53	nM	PubChem BioAssay data set
NPT383	Cell line	SNB-19	Homo sapiens	GI50	n.a.	712.85	nM	PubChem BioAssay data set
NPT82	Cell line	MDA-MB-231	Homo sapiens	GI50	n.a.	1137.63	nM	PubChem BioAssay data set
NPT385	Cell line	SR	Homo sapiens	GI50	n.a.	409.26	nM	PubChem BioAssay data set
NPT384	Cell line	TK-10	Homo sapiens	GI50	n.a.	167.11	nM	PubChem BioAssay data set
NPT323	Cell line	SW-620	Homo sapiens	GI50	n.a.	242.66	nM	PubChem BioAssay data set
NPT455	Cell line	NCI-H522	Homo sapiens	GI50	n.a.	39.26	nM	PubChem BioAssay data set
NPT387	Cell line	M14	Homo sapiens	GI50	n.a.	528.45	nM	PubChem BioAssay data set
NPT386	Cell line	KM12	Homo sapiens	GI50	n.a.	401.79	nM	PubChem BioAssay data set
NPT388	Cell line	NCI-H322M	Homo sapiens	GI50	n.a.	325.09	nM	PubChem BioAssay data set
NPT389	Cell line	RPMI-8226	Homo sapiens	GI50	n.a.	270.4	nM	PubChem BioAssay data set
NPT456	Cell line	OVCAR-4	Homo sapiens	GI50	n.a.	107.4	nM	PubChem BioAssay data set
NPT457	Cell line	BT-549	Homo sapiens	GI50	n.a.	207.01	nM	PubChem BioAssay data set
NPT390	Cell line	LOX IMVI	Homo sapiens	GI50	n.a.	184.08	nM	PubChem BioAssay data set
NPT147	Cell line	SK-MEL-2	Homo sapiens	GI50	n.a.	397.19	nM	PubChem BioAssay data set
NPT81	Cell line	A549	Homo sapiens	GI50	n.a.	80.54	nM	PubChem BioAssay data set
NPT391	Cell line	HCC 2998	Homo sapiens	GI50	n.a.	2079.7	nM	PubChem BioAssay data set
NPT392	Cell line	SNB-75	Homo sapiens	GI50	n.a.	399.94	nM	PubChem BioAssay data set
NPT148	Cell line	HCT-15	Homo sapiens	GI50	n.a.	192.31	nM	PubChem BioAssay data set
NPT395	Cell line	SF-268	Homo sapiens	GI50	n.a.	125.89	nM	PubChem BioAssay data set
NPT393	Cell line	HCT-116	Homo sapiens	GI50	n.a.	162.55	nM	PubChem BioAssay data set
NPT83	Cell line	MCF7	Homo sapiens	GI50	n.a.	463.45	nM	PubChem BioAssay data set
NPT394	Cell line	EKVX	Homo sapiens	GI50	n.a.	175.39	nM	PubChem BioAssay data set
NPT306	Cell line	PC-3	Homo sapiens	GI50	n.a.	203.24	nM	PubChem BioAssay data set
NPT146	Cell line	SK-OV-3	Homo sapiens	GI50	n.a.	114.29	nM	PubChem BioAssay data set
NPT396	Cell line	T47D	Homo sapiens	GI50	n.a.	383.71	nM	PubChem BioAssay data set
NPT397	Cell line	NCI-H460	Homo sapiens	GI50	n.a.	112.46	nM	PubChem BioAssay data set
NPT398	Cell line	UACC-62	Homo sapiens	GI50	n.a.	429.54	nM	PubChem BioAssay data set
NPT308	Cell line	CAKI-1	Homo sapiens	GI50	n.a.	101.62	nM	PubChem BioAssay data set
NPT400	Cell line	MDA-MB-435	Homo sapiens	GI50	n.a.	343.56	nM	PubChem BioAssay data set
NPT399	Cell line	SF-295	Homo sapiens	GI50	n.a.	133.35	nM	PubChem BioAssay data set
NPT402	Cell line	Hs-578T	Homo sapiens	GI50	n.a.	524.81	nM	PubChem BioAssay data set
NPT458	Cell line	IGROV-1	Homo sapiens	GI50	n.a.	447.71	nM	PubChem BioAssay data set
NPT401	Cell line	786-0	Homo sapiens	GI50	n.a.	137.09	nM	PubChem BioAssay data set
NPT403	Cell line	UACC-257	Homo sapiens	GI50	n.a.	369.83	nM	PubChem BioAssay data set
NPT404	Cell line	CCRF-CEM	Homo sapiens	GI50	n.a.	6531.31	nM	PubChem BioAssay data set
NPT405	Cell line	NCI-H226	Homo sapiens	GI50	n.a.	539.51	nM	PubChem BioAssay data set
NPT139	Cell line	HT-29	Homo sapiens	GI50	n.a.	233.35	nM	PubChem BioAssay data set
NPT170	Cell line	SK-MEL-28	Homo sapiens	GI50	n.a.	845.28	nM	PubChem BioAssay data set
NPT406	Cell line	RXF 393	Homo sapiens	GI50	n.a.	46.67	nM	PubChem BioAssay data set
NPT407	Cell line	COLO 205	Homo sapiens	GI50	n.a.	618.02	nM	PubChem BioAssay data set
NPT26691	Protein complex	N+/K+ ATPase alpha-4/beta-1	Rattus norvegicus	IC50	=	12.0	nM	PMID[29291372]

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 NPC180079 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	14482
0.1-0.2	31947
0.2-0.3	3121
0.3-0.4	102
0.4-0.5	104
0.5-0.6	52
0.6-0.7	29
0.7-0.8	2
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8667	High Similarity	NPC34390
0.8256	Intermediate Similarity	NPC329636
0.7949	Intermediate Similarity	NPC6108
0.7949	Intermediate Similarity	NPC89514
0.775	Intermediate Similarity	NPC484212
0.7407	Intermediate Similarity	NPC84949
0.7407	Intermediate Similarity	NPC480562
0.7407	Intermediate Similarity	NPC74945
0.7407	Intermediate Similarity	NPC10823
0.7407	Intermediate Similarity	NPC31354
0.7407	Intermediate Similarity	NPC69576
0.7284	Intermediate Similarity	NPC17896
0.7284	Intermediate Similarity	NPC469755
0.7284	Intermediate Similarity	NPC284406
0.7284	Intermediate Similarity	NPC197707
0.7284	Intermediate Similarity	NPC251866
0.7229	Intermediate Similarity	NPC483822
0.7191	Intermediate Similarity	NPC146857
0.6951	Remote Similarity	NPC219085
0.6707	Remote Similarity	NPC474418
0.6703	Remote Similarity	NPC469749
0.6667	Remote Similarity	NPC329675
0.6667	Remote Similarity	NPC194716
0.6556	Remote Similarity	NPC608063
0.6452	Remote Similarity	NPC247190
0.6374	Remote Similarity	NPC32793
0.6374	Remote Similarity	NPC116075
0.6235	Remote Similarity	NPC99728
0.6235	Remote Similarity	NPC87250
0.6235	Remote Similarity	NPC244402
0.6235	Remote Similarity	NPC50305
0.618	Remote Similarity	NPC469753
0.6154	Remote Similarity	NPC72772
0.6092	Remote Similarity	NPC157376
0.6092	Remote Similarity	NPC99080
0.6092	Remote Similarity	NPC142066
0.6092	Remote Similarity	NPC603972
0.6067	Remote Similarity	NPC9499
0.6067	Remote Similarity	NPC484202
0.6067	Remote Similarity	NPC471360
0.6067	Remote Similarity	NPC469751
0.6067	Remote Similarity	NPC471361
0.6067	Remote Similarity	NPC86159
0.6067	Remote Similarity	NPC469752
0.6067	Remote Similarity	NPC469754
0.6067	Remote Similarity	NPC70542
0.6023	Remote Similarity	NPC152615
0.5977	Remote Similarity	NPC84987
0.5977	Remote Similarity	NPC484211
0.5955	Remote Similarity	NPC250556
0.593	Remote Similarity	NPC158344
0.5889	Remote Similarity	NPC471359
0.5889	Remote Similarity	NPC93883
0.587	Remote Similarity	NPC103534
0.587	Remote Similarity	NPC44899
0.587	Remote Similarity	NPC304260
0.587	Remote Similarity	NPC29639
0.5789	Remote Similarity	NPC475629
0.5684	Remote Similarity	NPC475556
0.5684	Remote Similarity	NPC311706
0.5682	Remote Similarity	NPC471633
0.5667	Remote Similarity	NPC199428
0.5667	Remote Similarity	NPC109448
0.5667	Remote Similarity	NPC310341
0.5612	Remote Similarity	NPC329986
0.5612	Remote Similarity	NPC140092
0.5556	Remote Similarity	NPC469750
0.5543	Remote Similarity	NPC305574
0.5444	Remote Similarity	NPC309034
0.5435	Remote Similarity	NPC77319
0.5435	Remote Similarity	NPC471351
0.5435	Remote Similarity	NPC471355
0.5408	Remote Similarity	NPC59288
0.5408	Remote Similarity	NPC55532
0.5385	Remote Similarity	NPC486126
0.5385	Remote Similarity	NPC484210
0.5385	Remote Similarity	NPC477580
0.5375	Remote Similarity	NPC97487
0.5333	Remote Similarity	NPC99620
0.5326	Remote Similarity	NPC480914
0.5275	Remote Similarity	NPC486129
0.5269	Remote Similarity	NPC88668
0.5263	Remote Similarity	NPC72260
0.5248	Remote Similarity	NPC486138
0.5248	Remote Similarity	NPC276838
0.5244	Remote Similarity	NPC10232
0.5217	Remote Similarity	NPC480915
0.5204	Remote Similarity	NPC603096
0.52	Remote Similarity	NPC232785
0.52	Remote Similarity	NPC486139
0.5165	Remote Similarity	NPC473852
0.5161	Remote Similarity	NPC76572
0.5161	Remote Similarity	NPC193382
0.5158	Remote Similarity	NPC471354
0.5158	Remote Similarity	NPC27507
0.51	Remote Similarity	NPC125077
0.5054	Remote Similarity	NPC5311
0.5054	Remote Similarity	NPC77299
0.5054	Remote Similarity	NPC480906

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC180079 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5893
0.1-0.2	3139
0.2-0.3	104
0.3-0.4	1
0.4-0.5	6
0.5-0.6	4
0.6-0.7	1
0.7-0.8	2
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
0.7284	Intermediate Similarity	NPD7319	Approved
0.7024	Intermediate Similarity	NPD7516	Pre-clinical
0.6064	Remote Similarity	NPD8377	Phase 4
0.5955	Remote Similarity	NPD7507	Pre-clinical
0.5263	Remote Similarity	NPD8294	Phase 4
0.52	Remote Similarity	NPD8378	Pre-clinical
0.52	Remote Similarity	NPD8379	Approved

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