NPASS Compound

Natural Product: NPC270850

Natural Product ID	NPC270850
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Withacoagulin I
IUPAC Name	(2R)-2-[(1S)-1-[(8R,9S,10R,13S,14S,17R)-14,17-dihydroxy-10,13-dimethyl-1-oxo-2,7,8,9,11,12,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-1-hydroxyethyl]-4,5-dimethyl-2,3-dihydropyran-6-one
Synonyms	Withacoagulin I
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2333673
PubChem CID	71720665
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001560] Withanolides 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 72 76 0 0 0 0 0 0 0 0999 V2000 6.8942 -0.0169 -0.8210 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6516 0.2391 -0.0101 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7253 0.8794 1.1421 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0880 1.3367 1.5962 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5442 1.1147 1.9736 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6515 1.7296 3.0569 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3299 0.6106 1.4665 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4292 -0.4842 0.6297 C 0 0 2 0 0 0 0 0 0 0 0 0 4.3294 -0.2072 -0.5351 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1532 -1.2061 0.3170 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8051 -1.9806 1.6025 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0295 -0.3592 -0.1145 C 0 0 1 0 0 0 0 0 0 0 0 0 1.3757 0.5187 -1.2916 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0227 0.9601 -1.7915 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9670 -0.1344 -1.4652 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2729 0.3959 -1.0545 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3248 1.8794 -0.7427 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6756 2.2142 -0.2291 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6354 1.4136 0.0917 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9233 1.9213 0.5905 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6574 1.1742 1.3948 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2381 -0.1829 1.8306 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2820 -0.8169 0.8889 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2098 -2.0316 0.9049 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4298 -0.0762 -0.0488 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.9351 -0.4276 -1.4553 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9685 -0.2737 0.1005 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4775 -1.6580 0.2891 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9980 -1.4460 0.6837 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2132 -1.0350 -0.5336 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0582 -2.3707 -1.2565 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1366 -0.8202 -2.7013 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7417 0.5244 0.9408 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5620 -2.1927 -0.5798 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5642 -0.0793 -1.8783 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4165 -0.9257 -0.4726 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5839 0.8628 -0.7703 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0089 1.7214 2.6306 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5254 2.0557 0.8866 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7253 0.4231 1.5716 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0384 -1.2634 1.2260 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0062 0.6305 -1.1906 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4581 -1.1300 -1.1749 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0957 -1.4525 2.2354 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7321 -2.0744 2.2534 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5665 -3.0445 1.3861 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8643 1.4564 -0.9329 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8848 0.0061 -2.1039 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2523 1.9316 -1.3483 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1218 1.1518 -2.8806 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0042 0.3080 -1.9191 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1668 2.5116 -1.6386 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6322 2.1361 0.1050 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8596 3.2972 -0.1167 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2908 2.8939 0.3202 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6132 1.5228 1.7788 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7469 -0.1084 2.8220 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1226 -0.8420 1.9485 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3338 -1.2306 -1.9128 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9822 -0.8494 -1.4053 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0218 0.4684 -2.0953 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6632 0.2938 1.0322 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5635 -2.3247 -0.5660 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9205 -2.0963 1.2319 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0318 -0.6763 1.4802 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7073 -2.4583 1.0498 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7738 -2.2552 -2.0719 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9305 -2.5865 -1.7669 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2128 -3.1995 -0.5736 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0687 -1.1561 -2.7400 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1668 1.3913 0.8108 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1200 -2.8414 -0.0799 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 3 5 1 0 5 6 2 0 5 7 1 0 7 8 1 0 8 9 1 0 8 10 1 0 10 11 1 0 10 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 1 6 25 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 6 15 32 1 6 12 33 1 1 10 34 1 6 9 2 1 0 30 12 1 0 30 15 1 0 27 16 1 0 25 19 1 0 1 35 1 0 1 36 1 0 1 37 1 0 4 38 1 0 4 39 1 0 4 40 1 0 8 41 1 1 9 42 1 0 9 43 1 0 11 44 1 0 11 45 1 0 11 46 1 0 13 47 1 0 13 48 1 0 14 49 1 0 14 50 1 0 16 51 1 6 17 52 1 0 17 53 1 0 18 54 1 0 20 55 1 0 21 56 1 0 22 57 1 0 22 58 1 0 26 59 1 0 26 60 1 0 26 61 1 0 27 62 1 1 28 63 1 0 28 64 1 0 29 65 1 0 29 66 1 0 31 67 1 0 31 68 1 0 31 69 1 0 32 70 1 0 33 71 1 0 34 72 1 0 M END

Standard InCHIKey	HYSIDFWCYWFQMQ-IMANIDBLSA-N
Standard InCHI	InChI=1S/C28H38O6/c1-16-15-22(34-23(30)17(16)2)26(5,31)28(33)14-13-27(32)20-10-9-18-7-6-8-21(29)25(18,4)19(20)11-12-24(27,28)3/h6-7,9,19-20,22,31-33H,8,10-15H2,1-5H3/t19-,20+,22+,24-,25-,26-,27-,28+/m0/s1
SMILES	CC1=C(C)C(=O)O[C@H](C1)[C@@](C)([C@]1(CC[C@@]2([C@@H]3CC=C4C=CCC(=O)[C@]4(C)[C@H]3CC[C@]12C)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	470.27	Volume:	489.621 ? Van der Waals volume.
Dense:	0.96	LogP:	1.481 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.824 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.722 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	28.0
TPSA:	104.06 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	5.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.534	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.349	Fsp³:	0.714
MCE-18:	98.167 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.154	Fluc inhibitor:	0.082 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.007 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.013 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.43	Promiscuous compounds:	0.349

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.939	MDCK Permeability:	-4.722
Pgp-inhibitor:	0.002	Pgp-substrate:	0.902
PAMPA:	0.99 ? 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):	0.032
20% Bioavailability (F20%):	0.798	30% Bioavailability (F30%):	0.921
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.439	MRP1:	0.989
Plasma Protein Binding (PPB):	94.914%	Volume Distribution (VD):	0.221
Fu:	3.563% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.15
BSEP inhibitor:	0.83

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.087
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.708	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.024	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.241	CYP3A4-substrate:	0.177
CYP2B6-substrate:	0.133	CYP2C8-inhibitor:	0.988
HLM stability:	0.975 ? 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):

4.55

Half-life (T1/2):

2.169

ADMET: Toxicity

hERG Blockers:	0.048	hERG Blockers (10um):	0.251
Human Hepatotoxicity (H-HT):	0.679	Drug-induced Liver Injury (DILI):	0.08
AMES Toxicity:	0.34	Rat Oral Acute Toxicity:	0.373
Maximum Recommended Daily Dose:	0.693	Skin Sensitization:	0.987
Carcinogencity:	0.906	Eye Corrosion:	0.017
Eye Irritation:	0.519	Respiratory Toxicity:	0.545
Drug-induced Neurotoxicity:	0.253	Ototoxicity:	0.352
Hematotoxicity:	0.227	Drug-induced Nephrotoxicity:	0.724
Genotoxicity:	0.947	RPMI-8226 Immunitoxicity:	0.111
A549 Cytotoxicity:	0.325	Hek293 Cytotoxicity:	0.601
BCF:	0.535 ? 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:	3.127 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.492 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.901 ? 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
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	fruits	n.a.	n.a.	PMID[18952419]
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23316950]
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13927	Withania coagulans	Species	Solanaceae	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	2
Inhibition	2
Survival	2

Activity Type	# Activity
Cell line	4
Others	2

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
NPT113	Cell line	RAW264.7	Mus musculus	IC50	=	29000.0	nM	PMID[10560729]
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	=	69.8	%	PMID[17428663]
NPT2	Others	Unspecified	n.a.	IC50	=	8800.0	nM	PMID[23398362]
NPT2	Others	Unspecified	n.a.	Inhibition	=	89.9	%	PMID[19114678]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT71	Cell line	HEK293	Homo sapiens	Survival	=	89.4	%	PubChem BioAssay data set
NPT113	Cell line	RAW264.7	Mus musculus	Survival	=	100.0	%	PMID[17428663]

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 NPC270850 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	19340
0.1-0.2	26923
0.2-0.3	3469
0.3-0.4	90
0.4-0.5	18
0.5-0.6	11
0.6-0.7	3
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	Natural Product ID
1.0	High Similarity	NPC305260
0.7794	Intermediate Similarity	NPC484743
0.7	Intermediate Similarity	NPC153440
0.6667	Remote Similarity	NPC225826
0.6133	Remote Similarity	NPC107493
0.6053	Remote Similarity	NPC103045
0.5833	Remote Similarity	NPC173347
0.5584	Remote Similarity	NPC484742
0.5556	Remote Similarity	NPC5292
0.5513	Remote Similarity	NPC158285
0.5316	Remote Similarity	NPC79579
0.525	Remote Similarity	NPC125794
0.525	Remote Similarity	NPC171401
0.5185	Remote Similarity	NPC285729
0.5122	Remote Similarity	NPC5073
0.506	Remote Similarity	NPC484745
0.5056	Remote Similarity	NPC484715

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC270850 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6966
0.1-0.2	2084
0.2-0.3	100
0.3-0.4	0
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