NPASS Compound

Natural Product: NPC79579

Natural Product ID	NPC79579
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Coagulanolide
IUPAC Name	(2R)-2-[(1S)-1-hydroxy-1-[(8R,9S,10R,13S,14R,15S,17S)-14,15,17-trihydroxy-10,13-dimethyl-1-oxo-4,7,8,9,11,12,15,16-octahydrocyclopenta[a]phenanthren-17-yl]ethyl]-4,5-dimethyl-2,3-dihydropyran-6-one
Synonyms	coagulanolide
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL520391
PubChem CID	44562997
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 73 77 0 0 0 0 0 0 0 0999 V2000 5.3157 1.8213 2.4873 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7880 1.3684 1.1612 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3426 1.9285 0.1140 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4373 2.9562 0.2652 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8693 1.5410 -1.2004 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3712 2.0496 -2.2206 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8804 0.6233 -1.2803 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9055 0.4451 -0.2127 C 0 0 2 0 0 0 0 0 0 0 0 0 3.7291 0.3616 1.0374 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2174 -0.8226 -0.6187 C 0 0 1 0 0 0 0 0 0 0 0 0 3.3394 -1.8111 -0.8880 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2221 -1.4563 0.1904 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8330 -2.7868 -0.4444 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4643 -2.4809 -1.2197 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9162 -1.1704 -0.7476 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3506 -1.0338 -0.2998 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.3409 -1.4724 -1.3137 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5720 -0.6486 -1.3827 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8495 0.3423 -0.5683 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0980 1.1188 -0.7002 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8517 2.5757 -0.4617 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9234 3.0172 0.3680 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1170 2.0149 1.0706 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6336 2.3325 2.2104 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8544 0.6842 0.5157 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1631 -0.3171 1.6276 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5217 0.4858 -0.1128 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3652 1.1723 0.4549 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3476 0.3026 1.1929 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1108 -0.9745 0.5148 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.6711 -2.0669 1.4692 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7482 -0.1825 -1.7067 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2148 -2.4166 -2.5930 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8207 -1.8029 1.4427 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6959 -0.5221 -1.9087 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3627 2.9295 2.4306 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3580 1.4720 2.6468 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6448 1.5546 3.3136 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1163 2.8242 -0.6049 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9920 2.8234 1.1956 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9605 3.9639 0.2137 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3219 1.3517 -0.2440 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2517 -0.6399 1.1069 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0937 0.4208 1.9595 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2576 -2.6927 -0.1947 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1913 -2.2333 -1.8973 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3493 -1.3534 -0.8259 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5416 -3.1427 -1.1904 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6211 -3.5719 0.3088 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1882 -3.3131 -1.0942 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5977 -1.4681 0.6577 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9216 -1.5273 -2.3516 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6726 -2.5239 -1.0898 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2799 -0.8931 -2.1627 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8152 0.7124 0.0600 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5577 1.0284 -1.7014 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4597 3.2803 -0.9896 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7494 4.0842 0.5364 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5408 -1.2815 1.2199 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0555 0.1034 2.1806 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3736 -0.3995 2.3662 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6118 0.8428 -1.1883 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6034 2.0041 1.1635 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7318 1.6930 -0.3287 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5719 0.9305 1.3433 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7636 0.2213 2.2285 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1352 -2.5862 2.0123 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3393 -1.6490 2.2216 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2086 -2.8561 0.9164 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0934 -0.5221 -2.5471 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1810 -3.2517 -2.9441 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4753 -1.1984 2.1654 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4843 -0.3126 -2.4833 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 1 0 21 22 2 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 1 1 25 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 1 15 32 1 6 14 33 1 0 12 34 1 1 10 35 1 6 9 2 1 0 30 12 1 0 30 15 1 0 27 16 1 0 25 19 1 0 1 36 1 0 1 37 1 0 1 38 1 0 4 39 1 0 4 40 1 0 4 41 1 0 8 42 1 1 9 43 1 0 9 44 1 0 11 45 1 0 11 46 1 0 11 47 1 0 13 48 1 0 13 49 1 0 14 50 1 6 16 51 1 1 17 52 1 0 17 53 1 0 18 54 1 0 20 55 1 0 20 56 1 0 21 57 1 0 22 58 1 0 26 59 1 0 26 60 1 0 26 61 1 0 27 62 1 6 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 35 73 1 0 M END

Standard InCHIKey	XAEUKOBJPRGERY-VLXOZLMASA-N
Standard InCHI	InChI=1S/C28H38O7/c1-15-13-22(35-23(31)16(15)2)26(5,32)27(33)14-21(30)28(34)19-10-9-17-7-6-8-20(29)25(17,4)18(19)11-12-24(27,28)3/h6,8-9,18-19,21-22,30,32-34H,7,10-14H2,1-5H3/t18-,19+,21-,22+,24+,25-,26-,27-,28-/m0/s1
SMILES	CC1=C(C)C(=O)O[C@H](C1)[C@@](C)([C@@]1(C[C@@H]([C@]2([C@@H]3CC=C4CC=CC(=O)[C@]4(C)[C@H]3CC[C@]12C)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	486.26	Volume:	498.411 ? Van der Waals volume.
Dense:	0.976	LogP:	1.311 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.783 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.661 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	28.0
TPSA:	124.29 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	4.0	Rings:	5.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.349	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.527	Fsp³:	0.714
MCE-18:	100.75 ? 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:	0.405	Fluc inhibitor:	0.118 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.011 ? 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:	0.326	Promiscuous compounds:	0.33

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.604	MDCK Permeability:	-5.043
Pgp-inhibitor:	0.0	Pgp-substrate:	0.711
PAMPA:	0.996 ? 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):	0.013
20% Bioavailability (F20%):	0.583	30% Bioavailability (F30%):	0.666
50% Bioavailability (F50%):	0.99

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.486	MRP1:	0.987
Plasma Protein Binding (PPB):	89.903%	Volume Distribution (VD):	-0.015
Fu:	9.852% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.072
BSEP inhibitor:	0.829

ADMET: Metabolism

CYP1A2-inhibitor:	0.986	CYP1A2-substrate:	0.223
CYP2C19-inhibitor:	0.461	CYP2C19-substrate:	0.05
CYP2C9-inhibitor:	0.219	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.083	CYP2D6-substrate:	0.013
CYP3A4-inhibitor:	0.092	CYP3A4-substrate:	0.933
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.639 ? 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):

3.234

Half-life (T1/2):

2.56

ADMET: Toxicity

hERG Blockers:	0.017	hERG Blockers (10um):	0.096
Human Hepatotoxicity (H-HT):	0.651	Drug-induced Liver Injury (DILI):	0.341
AMES Toxicity:	0.585	Rat Oral Acute Toxicity:	0.404
Maximum Recommended Daily Dose:	0.735	Skin Sensitization:	0.994
Carcinogencity:	0.848	Eye Corrosion:	0.004
Eye Irritation:	0.473	Respiratory Toxicity:	0.718
Drug-induced Neurotoxicity:	0.152	Ototoxicity:	0.53
Hematotoxicity:	0.486	Drug-induced Nephrotoxicity:	0.728
Genotoxicity:	0.966	RPMI-8226 Immunitoxicity:	0.132
A549 Cytotoxicity:	0.409	Hek293 Cytotoxicity:	0.421
BCF:	0.56 ? 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:	3.203 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.687 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.043 ? 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
Activity	2

Activity Type	# Activity
Organism	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

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Activity	=	28.1	%	PMID[23398362]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Activity	=	14.7	%	PMID[23398362]

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 NPC79579 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	17945
0.1-0.2	27005
0.2-0.3	4729
0.3-0.4	124
0.4-0.5	28
0.5-0.6	14
0.6-0.7	7
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8028	Intermediate Similarity	NPC484717
0.7647	Intermediate Similarity	NPC153440
0.6712	Remote Similarity	NPC107493
0.6711	Remote Similarity	NPC5292
0.6622	Remote Similarity	NPC103045
0.6447	Remote Similarity	NPC329671
0.6351	Remote Similarity	NPC176840
0.6351	Remote Similarity	NPC190286
0.6351	Remote Similarity	NPC484742
0.5926	Remote Similarity	NPC484718
0.5921	Remote Similarity	NPC225826
0.5897	Remote Similarity	NPC470961
0.5854	Remote Similarity	NPC484725
0.5844	Remote Similarity	NPC191620
0.557	Remote Similarity	NPC46570
0.557	Remote Similarity	NPC44428
0.557	Remote Similarity	NPC78691
0.5316	Remote Similarity	NPC270850
0.5316	Remote Similarity	NPC305260
0.5309	Remote Similarity	NPC285729
0.525	Remote Similarity	NPC158285
0.5208	Remote Similarity	NPC484726
0.5125	Remote Similarity	NPC486565

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC79579 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6537
0.1-0.2	2437
0.2-0.3	176
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