NPASS Compound

Natural Product: NPC530777

Natural Product ID	NPC530777
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(1R,3aS,3bS,9aR,11aS)-1-[(1S)-1,2-Dihydroxyethyl]-1,10-dihydroxy-9a,11a-dimethyl-1H,2H,3H,3aH,3bH,4H,5H,7H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthren-7-one
IUPAC Name	(8~{R},9~{R},10~{R},11~{R},13~{S},14~{R},17~{R})-17-[(1~{S})-1,2-dihydroxyethyl]-11,17-dihydroxy-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6~{H}-cyclopenta[a]phenanthren-3-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001295] Hydroxysteroids [CHEMONTID:0003095] 21-hydroxysteroids

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 -3.6938 -1.5639 -0.1207 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9693 -0.2527 0.2687 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.5915 0.2020 1.5145 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2446 1.3249 1.6564 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3840 2.2194 0.5104 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9946 3.3074 0.5705 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7698 1.7953 -0.7536 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1215 0.6644 -0.8650 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5190 0.2944 -2.1703 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3976 -0.7234 -1.9776 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6501 -0.2978 -0.7343 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5015 -0.5508 0.5082 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8874 0.2143 1.6257 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.4877 1.4694 1.6898 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5839 0.4428 1.4811 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3324 -0.5525 0.6774 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8546 -1.7125 1.4738 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6103 -1.0849 -0.5227 C 0 0 2 0 0 0 0 0 0 0 0 0 1.5495 -1.1168 -1.6722 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8971 -0.5756 -1.1768 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5121 0.1935 0.0357 C 0 0 1 0 0 0 0 0 0 0 0 0 1.9711 1.4225 -0.3886 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6115 0.4800 1.0030 C 0 0 1 0 0 0 0 0 0 0 0 0 4.1819 -0.6976 1.4315 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6909 1.2732 0.3070 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2550 0.6352 -0.7756 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0432 -1.5140 -1.1707 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5967 -1.7218 0.4975 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0039 -2.4236 0.0583 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5312 -0.4141 2.4272 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6936 1.6209 2.6090 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8643 2.4473 -1.6093 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2754 -0.0729 -2.8908 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0807 1.2060 -2.6059 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7694 -1.7508 -1.8932 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7460 -0.6460 -2.8461 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4498 0.7865 -0.8068 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4233 -1.6636 0.6688 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1271 -0.2728 2.6168 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9172 2.1935 1.3757 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8062 1.4960 1.1392 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0150 0.4186 2.5259 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5843 -2.2701 0.8517 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2486 -1.4270 2.4742 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9579 -2.3876 1.6338 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2807 -2.1441 -0.3097 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2581 -0.5115 -2.5419 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7812 -2.1759 -1.9904 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3278 0.1166 -1.9331 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5802 -1.3881 -0.8834 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3683 1.6671 -1.2755 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2579 1.1052 1.8638 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7016 -0.5816 2.2606 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2652 2.2455 -0.0285 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5082 1.4353 1.0526 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7429 -0.1834 -0.4997 H 0 0 0 0 0 0 0 0 0 0 0 0 2 1 1 6 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 5 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 13 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 6 21 23 1 0 23 24 1 0 23 25 1 0 25 26 1 0 8 2 1 0 18 11 1 0 12 2 1 0 21 16 1 0 1 27 1 0 1 28 1 0 1 29 1 0 3 30 1 0 4 31 1 0 7 32 1 0 9 33 1 0 9 34 1 0 10 35 1 0 10 36 1 0 11 37 1 6 12 38 1 1 13 39 1 1 14 40 1 0 15 41 1 0 15 42 1 0 17 43 1 0 17 44 1 0 17 45 1 0 18 46 1 1 19 47 1 0 19 48 1 0 20 49 1 0 20 50 1 0 22 51 1 0 23 52 1 1 24 53 1 0 25 54 1 0 25 55 1 0 26 56 1 0 M END

Standard InCHIKey	LCOVYWIXMAJCDS-UKBVDAKRSA-N
Standard InCHI	InChI=1S/C21H30O5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h5,7,9,14-18,22,24-26H,3-4,6,8,10-11H2,1-2H3/t14-,15-,16-,17+,18+,19+,20+,21+/m1/s1
SMILES	C[C@]12C=CC(=O)C=C1CC[C@H]1[C@H]2[C@H](O)C[C@@]2(C)[C@@H]1CC[C@]2(O)[C@@H](O)CO

Calculated Properties

Physi-Chem Properties

Molecular Weight:	362.21	Volume:	373.588 ? Van der Waals volume.
Dense:	0.97	LogP:	1.18 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.59 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.01 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	21.0
TPSA:	97.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	4.0	Rings:	4.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.594	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.675	Fsp³:	0.762
MCE-18:	74.162 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.457	Fluc inhibitor:	0.029 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.099 ? 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:	0.263	Promiscuous compounds:	0.567

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.624	MDCK Permeability:	-5.011
Pgp-inhibitor:	0.01	Pgp-substrate:	0.062
PAMPA:	0.992 ? 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):	0.008
20% Bioavailability (F20%):	0.161	30% Bioavailability (F30%):	0.1
50% Bioavailability (F50%):	0.842

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.897	MRP1:	0.27
Plasma Protein Binding (PPB):	86.975%	Volume Distribution (VD):	0.165
Fu:	16.002% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.984
OATP1B3 inhibitor:	0.927	BCRP inhibitor:	0.04
BSEP inhibitor:	0.819

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.006	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.562	CYP3A4-substrate:	0.988
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.988
HLM stability:	0.023 ? 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):

4.21

Half-life (T1/2):

1.711

ADMET: Toxicity

hERG Blockers:	0.037	hERG Blockers (10um):	0.171
Human Hepatotoxicity (H-HT):	0.64	Drug-induced Liver Injury (DILI):	0.028
AMES Toxicity:	0.463	Rat Oral Acute Toxicity:	0.639
Maximum Recommended Daily Dose:	0.815	Skin Sensitization:	0.966
Carcinogencity:	0.886	Eye Corrosion:	0.005
Eye Irritation:	0.871	Respiratory Toxicity:	0.601
Drug-induced Neurotoxicity:	0.109	Ototoxicity:	0.573
Hematotoxicity:	0.086	Drug-induced Nephrotoxicity:	0.384
Genotoxicity:	0.788	RPMI-8226 Immunitoxicity:	0.127
A549 Cytotoxicity:	0.087	Hek293 Cytotoxicity:	0.389
BCF:	0.622 ? 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:	3.291 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.894 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.195 ? 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
NPO55968	Streptomyces roseochromogenes TS79	Genus	Streptomycetaceae	Bacteria	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 NPC530777 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	20058
0.1-0.2	27610
0.2-0.3	2120
0.3-0.4	53
0.4-0.5	14
0.5-0.6	2
0.6-0.7	1
0.7-0.8	1
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
0.7544	Intermediate Similarity	NPC334061
0.6667	Remote Similarity	NPC44063
0.5538	Remote Similarity	NPC169375
0.5303	Remote Similarity	NPC144956

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC530777 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7120
0.1-0.2	1801
0.2-0.3	126
0.3-0.4	64
0.4-0.5	21
0.5-0.6	10
0.6-0.7	6
0.7-0.8	1
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
0.7544	Intermediate Similarity	NPD4696	Phase 4
0.6667	Remote Similarity	NPD5697	Phase 4
0.6562	Remote Similarity	NPD4632	Approved
0.6557	Remote Similarity	NPD5211	Phase 2
0.6462	Remote Similarity	NPD4729	Approved
0.6462	Remote Similarity	NPD6899	Phase 4
0.6364	Remote Similarity	NPD4730	Phase 4
0.5714	Remote Similarity	NPD6079	Phase 4
0.5667	Remote Similarity	NPD4195	Phase 4
0.56	Remote Similarity	NPD8297	Phase 4
0.5556	Remote Similarity	NPD6370	Phase 4
0.5385	Remote Similarity	NPD4629	Phase 4
0.5303	Remote Similarity	NPD5286	Phase 4
0.5147	Remote Similarity	NPD4633	Phase 4
0.5139	Remote Similarity	NPD6054	Phase 4
0.506	Remote Similarity	NPD7057	Phase 3
0.506	Remote Similarity	NPD7058	Phase 2

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