NPASS Compound

Natural Product: NPC326627

Natural Product ID	NPC326627
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	17-Hydroxy-17-(2-Hydroxyacetyl)-10,13-Dimethyl-2,6,7,8,9,11,12,14,15,16-Decahydro-1H-Cyclopenta[A]Phenanthren-3-One
IUPAC Name	17-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1705958
PubChem CID	227112
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 55 58 0 0 0 0 0 0 0 0999 V2000 -2.5996 1.5153 1.5023 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3148 0.6553 0.2743 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9068 1.3897 -0.9025 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3834 1.6924 -0.6776 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0110 0.5040 -0.0320 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2166 0.5592 0.3183 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2636 -0.7248 0.2055 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9532 -0.6569 0.3548 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0794 -1.8408 0.5929 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9543 -1.8797 -0.4248 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3566 -0.5625 -0.7129 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8199 0.5958 0.1223 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0993 0.8159 1.4128 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3878 0.6455 1.3599 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8217 -0.5283 0.5443 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1391 -0.4656 -0.7427 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8570 -1.3422 -1.6531 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2664 -1.3543 -1.1095 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2695 -0.5275 0.1430 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9008 0.7935 0.0326 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5182 1.1833 1.0420 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9128 1.7211 -1.0985 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4780 1.2552 -2.3071 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9430 -1.2841 1.1586 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6050 -1.7724 1.3666 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6797 1.7443 1.6118 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1241 2.5256 1.3312 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2266 1.0849 2.4318 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3380 2.3114 -1.1358 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8588 0.7549 -1.8146 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8901 1.8463 -1.6536 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5355 2.6162 -0.0921 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7405 -1.6912 0.2644 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7488 -1.8849 1.6287 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7034 -2.7431 0.4285 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4341 -2.3413 -1.3482 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2591 -2.6822 -0.1097 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6366 -0.3266 -1.7979 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5711 1.5185 -0.4912 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2908 1.8143 1.8547 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4858 0.0771 2.1452 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8186 1.6125 1.0297 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7440 0.5008 2.4016 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2925 0.6025 -1.1061 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4494 -2.3640 -1.7853 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8255 -0.9029 -2.6944 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9364 -0.9812 -1.9077 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6117 -2.4044 -0.9019 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2951 2.6507 -0.8941 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9414 2.1690 -1.2650 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7441 1.7555 -2.7113 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8554 -1.5224 0.8048 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6296 -1.7612 1.8920 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8913 -2.7048 0.8926 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3471 -1.6615 2.2221 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 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 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 2 0 20 22 1 0 22 23 1 0 19 24 1 0 15 25 1 0 8 2 1 0 12 2 1 0 16 11 1 0 19 15 1 0 1 26 1 0 1 27 1 0 1 28 1 0 3 29 1 0 3 30 1 0 4 31 1 0 4 32 1 0 7 33 1 0 9 34 1 0 9 35 1 0 10 36 1 0 10 37 1 0 11 38 1 0 12 39 1 0 13 40 1 0 13 41 1 0 14 42 1 0 14 43 1 0 16 44 1 0 17 45 1 0 17 46 1 0 18 47 1 0 18 48 1 0 22 49 1 0 22 50 1 0 23 51 1 0 24 52 1 0 25 53 1 0 25 54 1 0 25 55 1 0 M END

Standard InCHIKey	WHBHBVVOGNECLV-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C21H30O4/c1-19-8-5-14(23)11-13(19)3-4-15-16(19)6-9-20(2)17(15)7-10-21(20,25)18(24)12-22/h11,15-17,22,25H,3-10,12H2,1-2H3
SMILES	CC12CCC(=O)C=C1CCC3C2CCC4(C3CCC4(C(=O)CO)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	346.21	Volume:	364.798 ? Van der Waals volume.
Dense:	0.949	LogP:	2.541 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.733 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.139 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	22.0
TPSA:	74.6 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.806	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.128	Fsp³:	0.81
MCE-18:	73.895 ? 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:	0.006	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.003 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.034 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.342	Promiscuous compounds:	0.356

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.294	MDCK Permeability:	-4.78
Pgp-inhibitor:	0.25	Pgp-substrate:	0.019
PAMPA:	0.087 ? 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):	0.003
20% Bioavailability (F20%):	0.016	30% Bioavailability (F30%):	0.016
50% Bioavailability (F50%):	0.133

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.565	MRP1:	0.984
Plasma Protein Binding (PPB):	84.798%	Volume Distribution (VD):	-0.345
Fu:	8.991% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.001
OATP1B3 inhibitor:	0.025	BCRP inhibitor:	0.006
BSEP inhibitor:	0.991

ADMET: Metabolism

CYP1A2-inhibitor:	0.375	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.998	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.827	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.017	CYP2C8-inhibitor:	0.452
HLM stability:	0.904 ? 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):

4.97

Half-life (T1/2):

2.252

ADMET: Toxicity

hERG Blockers:	0.075	hERG Blockers (10um):	0.271
Human Hepatotoxicity (H-HT):	0.757	Drug-induced Liver Injury (DILI):	0.102
AMES Toxicity:	0.212	Rat Oral Acute Toxicity:	0.11
Maximum Recommended Daily Dose:	0.737	Skin Sensitization:	0.036
Carcinogencity:	0.665	Eye Corrosion:	0.0
Eye Irritation:	0.063	Respiratory Toxicity:	0.345
Drug-induced Neurotoxicity:	0.194	Ototoxicity:	0.842
Hematotoxicity:	0.261	Drug-induced Nephrotoxicity:	0.059
Genotoxicity:	0.164	RPMI-8226 Immunitoxicity:	0.049
A549 Cytotoxicity:	0.043	Hek293 Cytotoxicity:	0.292
BCF:	0.814 ? 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:	3.788 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.447 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.446 ? 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
NPO30940	Bas taurus	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCM_Taiwan]

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
Potency	4
Inhibition	5

Activity Type	# Activity
Individual protein	4
Organism	5

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT152	Individual protein	Nuclear factor erythroid 2-related factor 2	Homo sapiens	Potency	n.a.	6513.1	nM	PubChem BioAssay data set
NPT135	Individual protein	Chromobox protein homolog 1	Homo sapiens	Potency	n.a.	79432.8	nM	PubChem BioAssay data set
NPT10	Individual protein	Geminin	Homo sapiens	Potency	n.a.	115.8	nM	PubChem BioAssay data set
NPT160	Individual protein	TAR DNA-binding protein 43	Homo sapiens	Potency	n.a.	354.8	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20	Organism	Candida albicans	Candida albicans	Inhibition	=	3.12	%	DOI[10.6019/CHEMBL4513141]
NPT173	Organism	Klebsiella pneumoniae	Klebsiella pneumoniae	Inhibition	=	8.14	%	DOI[10.6019/CHEMBL4513141]
NPT19	Organism	Escherichia coli	Escherichia coli	Inhibition	=	-7.68	%	DOI[10.6019/CHEMBL4513141]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	Inhibition	=	7.63	%	DOI[10.6019/CHEMBL4513141]
NPT747	Organism	Acinetobacter baumannii	Acinetobacter baumannii	Inhibition	=	14.88	%	DOI[10.6019/CHEMBL4513141]

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 NPC326627 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	18997
0.1-0.2	27595
0.2-0.3	3133
0.3-0.4	80
0.4-0.5	24
0.5-0.6	21
0.6-0.7	1
0.7-0.8	4
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC310010
0.8571	High Similarity	NPC144258
0.7455	Intermediate Similarity	NPC233118
0.7321	Intermediate Similarity	NPC18509
0.7321	Intermediate Similarity	NPC319582
0.614	Remote Similarity	NPC237712
0.5789	Remote Similarity	NPC214043
0.5789	Remote Similarity	NPC227064
0.5789	Remote Similarity	NPC85774
0.5789	Remote Similarity	NPC329043
0.5789	Remote Similarity	NPC58841
0.5789	Remote Similarity	NPC161423
0.569	Remote Similarity	NPC327115
0.5636	Remote Similarity	NPC139397
0.5536	Remote Similarity	NPC307176
0.5536	Remote Similarity	NPC321874
0.5439	Remote Similarity	NPC2634
0.5439	Remote Similarity	NPC265782
0.5439	Remote Similarity	NPC251929
0.5424	Remote Similarity	NPC115023
0.5333	Remote Similarity	NPC149203
0.5254	Remote Similarity	NPC282593
0.5217	Remote Similarity	NPC478926
0.5167	Remote Similarity	NPC35734
0.5167	Remote Similarity	NPC159577
0.5167	Remote Similarity	NPC602429
0.5156	Remote Similarity	NPC334061

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC326627 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6730
0.1-0.2	2162
0.2-0.3	143
0.3-0.4	61
0.4-0.5	31
0.5-0.6	16
0.6-0.7	0
0.7-0.8	4
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD4753	Phase 2
0.7647	Intermediate Similarity	NPD4221	Phase 4
0.7321	Intermediate Similarity	NPD4754	Approved
0.7321	Intermediate Similarity	NPD4755	Phase 4
0.7222	Intermediate Similarity	NPD4693	Phase 3
0.5965	Remote Similarity	NPD4197	Pre-clinical
0.5862	Remote Similarity	NPD5329	Approved
0.5789	Remote Similarity	NPD3666	Phase 4
0.5536	Remote Similarity	NPD4747	Phase 4
0.5469	Remote Similarity	NPD6083	Phase 4
0.5469	Remote Similarity	NPD6084	Phase 2
0.5455	Remote Similarity	NPD5696	Phase 4
0.5455	Remote Similarity	NPD5739	Phase 4
0.5439	Remote Similarity	NPD4691	Approved
0.5303	Remote Similarity	NPD4700	Phase 2
0.5294	Remote Similarity	NPD4767	Approved
0.5254	Remote Similarity	NPD4223	Phase 3
0.5217	Remote Similarity	NPD4768	Phase 4
0.5156	Remote Similarity	NPD4629	Phase 4
0.5156	Remote Similarity	NPD4696	Phase 4
0.5082	Remote Similarity	NPD5280	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