NPASS Compound

Natural Product: NPC493040

Natural Product ID	NPC493040
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5alpha-pregnene-3beta-ol
IUPAC Name	(3~{S},5~{S},8~{R},9~{S},10~{S},13~{R},14~{S},17~{R})-10,13-dimethyl-17-vinyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1~{H}-cyclopenta[a]phenanthren-3-ol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 56 59 0 0 0 0 0 0 0 0999 V2000 -5.4057 -0.9788 1.5727 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5953 -1.0944 0.5462 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7870 0.0253 0.0422 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.7691 1.2138 1.0158 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4343 1.9141 0.7065 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7271 1.0216 -0.2470 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2475 0.9081 -0.0508 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4041 2.1922 -0.4404 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8949 2.1495 -0.4992 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4835 0.8679 -0.9544 C 0 0 1 0 0 0 0 0 0 0 0 0 3.9239 0.8070 -0.5603 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6053 -0.4481 -1.0177 C 0 0 1 0 0 0 0 0 0 0 0 0 5.8307 -0.5256 -0.3228 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8445 -1.6944 -0.7193 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3772 -1.6055 -0.9371 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7766 -0.3444 -0.3889 C 0 0 1 0 0 0 0 0 0 0 0 0 1.9152 -0.3167 1.1042 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3366 -0.2102 -0.8479 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3916 -1.4948 -0.8125 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8789 -1.3081 -0.9173 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3179 -0.3358 0.1043 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0139 -0.7746 1.4959 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5147 -0.0477 2.0954 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0124 -1.8058 1.9574 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4733 -2.0449 -0.0006 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0941 0.3887 -0.9475 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6310 1.8765 0.8911 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7370 0.8630 2.0769 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8232 2.0086 1.6292 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6697 2.9114 0.2754 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0135 1.2194 -1.2968 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0771 0.7715 1.0511 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1321 2.9495 0.3512 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0638 2.6023 -1.3788 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2310 2.9561 -1.1860 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3523 2.4088 0.4953 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4427 0.7518 -2.0710 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0722 0.9893 0.5262 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4398 1.6661 -1.0787 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8975 -0.3788 -2.1002 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6271 -0.5579 0.6449 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2365 -2.4929 -1.4161 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1001 -2.0843 0.3031 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0938 -1.7610 -2.0053 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8982 -2.4560 -0.3861 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9267 -0.7288 1.3543 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1930 -0.9919 1.6249 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9046 0.7091 1.5321 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3680 0.1375 -1.9213 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0857 -2.1578 0.0255 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0928 -2.0735 -1.7379 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0662 -0.8508 -1.9307 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4316 -2.2603 -0.9231 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1692 -1.4625 1.6020 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9165 -1.3514 1.8569 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8679 0.0581 2.2145 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 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 12 13 1 0 12 14 1 0 14 15 1 0 15 16 1 0 16 17 1 1 16 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 1 21 3 1 0 21 6 1 0 18 7 1 0 16 10 1 0 1 23 1 0 1 24 1 0 2 25 1 0 3 26 1 6 4 27 1 0 4 28 1 0 5 29 1 0 5 30 1 0 6 31 1 6 7 32 1 1 8 33 1 0 8 34 1 0 9 35 1 0 9 36 1 0 10 37 1 6 11 38 1 0 11 39 1 0 12 40 1 6 13 41 1 0 14 42 1 0 14 43 1 0 15 44 1 0 15 45 1 0 17 46 1 0 17 47 1 0 17 48 1 0 18 49 1 6 19 50 1 0 19 51 1 0 20 52 1 0 20 53 1 0 22 54 1 0 22 55 1 0 22 56 1 0 M END

Standard InCHIKey	JKTCVURCUCFDGC-DDYSHWNRSA-N
Standard InCHI	InChI=1S/C21H34O/c1-4-14-6-8-18-17-7-5-15-13-16(22)9-11-21(15,3)19(17)10-12-20(14,18)2/h4,14-19,22H,1,5-13H2,2-3H3/t14-,15-,16-,17-,18-,19-,20+,21-/m0/s1
SMILES	C=C[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	302.26	Volume:	343.7 ? Van der Waals volume.
Dense:	0.879	LogP:	5.897 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.437 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.78 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	21.0
TPSA:	20.23 ? Topological Polar Surface Area.	H-Bond Acceptor:	1.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	1.0

MedChem Properties

QED Drug-Likeness Score:	0.661	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.223	Fsp³:	0.905
MCE-18:	68.4 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.568	Fluc inhibitor:	0.058 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.015 ? 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:	0.862	Promiscuous compounds:	0.251

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.773	MDCK Permeability:	-4.884
Pgp-inhibitor:	0.522	Pgp-substrate:	0.068
PAMPA:	0.047 ? 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):	0.001
20% Bioavailability (F20%):	0.153	30% Bioavailability (F30%):	0.39
50% Bioavailability (F50%):	0.904

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.843	MRP1:	0.045
Plasma Protein Binding (PPB):	92.341%	Volume Distribution (VD):	-0.081
Fu:	8.21% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.959
BSEP inhibitor:	0.67

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.084
CYP2C19-inhibitor:	0.674	CYP2C19-substrate:	0.008
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.882
CYP2D6-inhibitor:	0.714	CYP2D6-substrate:	0.575
CYP3A4-inhibitor:	0.998	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.975
HLM stability:	0.859 ? 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):

17.189

Half-life (T1/2):

1.651

ADMET: Toxicity

hERG Blockers:	0.179	hERG Blockers (10um):	0.397
Human Hepatotoxicity (H-HT):	0.524	Drug-induced Liver Injury (DILI):	0.394
AMES Toxicity:	0.133	Rat Oral Acute Toxicity:	0.074
Maximum Recommended Daily Dose:	0.853	Skin Sensitization:	0.978
Carcinogencity:	0.962	Eye Corrosion:	0.983
Eye Irritation:	1.0	Respiratory Toxicity:	0.97
Drug-induced Neurotoxicity:	0.059	Ototoxicity:	0.281
Hematotoxicity:	0.379	Drug-induced Nephrotoxicity:	0.454
Genotoxicity:	0.019	RPMI-8226 Immunitoxicity:	0.015
A549 Cytotoxicity:	0.204	Hek293 Cytotoxicity:	0.791
BCF:	2.536 ? 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:	4.038 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.787 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.696 ? 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
NPO48028	Muricea sp.	Genus	Plexauridae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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

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

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 NPC493040 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	20649
0.1-0.2	24917
0.2-0.3	3846
0.3-0.4	347
0.4-0.5	68
0.5-0.6	9
0.6-0.7	13
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	Natural Product ID
0.7674	Intermediate Similarity	NPC103822
0.7317	Intermediate Similarity	NPC114891
0.7209	Intermediate Similarity	NPC320549
0.7209	Intermediate Similarity	NPC156277
0.7209	Intermediate Similarity	NPC58057
0.7209	Intermediate Similarity	NPC151018
0.7045	Intermediate Similarity	NPC71460
0.7045	Intermediate Similarity	NPC218585
0.6889	Remote Similarity	NPC148174
0.6739	Remote Similarity	NPC254340
0.6531	Remote Similarity	NPC167702
0.6531	Remote Similarity	NPC192456
0.6531	Remote Similarity	NPC280026
0.6364	Remote Similarity	NPC281540
0.6364	Remote Similarity	NPC159654
0.6364	Remote Similarity	NPC167995
0.6364	Remote Similarity	NPC118937
0.617	Remote Similarity	NPC327728
0.617	Remote Similarity	NPC6120
0.617	Remote Similarity	NPC131892
0.617	Remote Similarity	NPC213178
0.5818	Remote Similarity	NPC323180
0.5517	Remote Similarity	NPC320478
0.5273	Remote Similarity	NPC477818
0.5172	Remote Similarity	NPC155924
0.5172	Remote Similarity	NPC248944
0.5172	Remote Similarity	NPC7479
0.5172	Remote Similarity	NPC257296
0.5091	Remote Similarity	NPC4209
0.5082	Remote Similarity	NPC481427

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC493040 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7017
0.1-0.2	1945
0.2-0.3	147
0.3-0.4	22
0.4-0.5	10
0.5-0.6	4
0.6-0.7	3
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
0.7209	Intermediate Similarity	NPD4808	Phase 2
0.7209	Intermediate Similarity	NPD4809	Phase 4
0.6531	Remote Similarity	NPD6113	Clinical (unspecified phase)
0.617	Remote Similarity	NPD3699	Clinical (unspecified phase)
0.617	Remote Similarity	NPD3700	Clinical (unspecified phase)
0.5714	Remote Similarity	NPD4787	Phase 1
0.5686	Remote Similarity	NPD3671	Phase 1
0.5172	Remote Similarity	NPD6928	Phase 2
0.5091	Remote Similarity	NPD6117	Phase 4

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