NPASS Compound

Natural Product: NPC318475

Natural Product ID	NPC318475
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	YMCWOAZGWMZGQT-KYQPOWKGSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	15708880
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0003568] Androstane steroids [CHEMONTID:0001467] Androgens 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 50 53 0 0 0 0 0 0 0 0999 V2000 2.5297 1.2908 0.9727 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9478 0.0811 0.2361 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4552 -1.1084 1.0633 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9389 -1.1735 1.0935 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6008 -0.6433 -0.1042 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8324 -0.4181 -0.1867 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7479 -0.3613 -1.2814 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4872 -0.0166 -1.1401 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6068 0.2595 -2.2641 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2866 -0.4645 -2.1734 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2927 -0.5391 -0.7913 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4794 0.1852 0.2718 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0086 1.6150 0.2373 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3312 1.5997 0.9865 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2376 0.6485 0.2973 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7264 -0.0897 -0.8665 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6213 -1.3221 -0.9654 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3772 -1.4084 0.3260 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8266 -0.3582 1.2651 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8762 0.2324 1.9671 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2407 -2.6461 0.9547 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4407 1.4774 -0.1893 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5635 1.0316 1.3589 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9499 1.4501 1.9037 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6690 2.1585 0.3354 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0908 -0.9208 2.0971 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0454 -2.0582 0.6831 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3823 -0.7125 2.0178 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2481 -2.2582 1.1702 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1640 -0.4381 -2.2774 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0567 -0.0616 -3.2506 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4005 1.3516 -2.4163 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3675 -1.4880 -2.6466 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4044 0.0844 -2.8818 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2949 -1.6099 -0.4974 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1546 -0.2410 1.2694 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2894 1.9101 -0.8126 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6835 2.3573 0.6277 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1551 1.3274 2.0676 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6894 2.6470 1.0035 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8725 0.4795 -1.8038 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3389 -1.2420 -1.7932 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0048 -2.2490 -1.0504 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4720 -1.1817 0.1653 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0858 -0.7444 1.9715 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5901 1.0864 2.3934 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4882 -2.5993 1.5754 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7147 2.1636 0.6207 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0499 2.0979 -1.0220 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2594 0.8190 -0.5175 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 18 21 1 0 15 22 1 0 8 2 1 0 12 2 1 0 16 11 1 0 19 15 1 0 1 23 1 0 1 24 1 0 1 25 1 0 3 26 1 0 3 27 1 0 4 28 1 0 4 29 1 0 7 30 1 0 9 31 1 0 9 32 1 0 10 33 1 0 10 34 1 0 11 35 1 0 12 36 1 0 13 37 1 0 13 38 1 0 14 39 1 0 14 40 1 0 16 41 1 0 17 42 1 0 17 43 1 0 18 44 1 0 19 45 1 0 20 46 1 0 21 47 1 0 22 48 1 0 22 49 1 0 22 50 1 0 M END

Standard InCHIKey	YMCWOAZGWMZGQT-KYQPOWKGSA-N
Standard InCHI	InChI=1S/C19H28O3/c1-18-7-5-12(20)9-11(18)3-4-13-14(18)6-8-19(2)15(13)10-16(21)17(19)22/h9,13-17,21-22H,3-8,10H2,1-2H3/t13-,14+,15+,16+,17+,18+,19+/m1/s1
SMILES	CC12CCC(=O)C=C1CCC3C2CCC4(C3CC(C4O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	304.2	Volume:	324.052 ? Van der Waals volume.
Dense:	0.939	LogP:	2.298 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.664 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.072 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	21.0
TPSA:	57.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.723	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.165	Fsp³:	0.842
MCE-18:	70.0 ? 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:	0.144	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.034 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.006 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.382	Promiscuous compounds:	0.02

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.39	MDCK Permeability:	-4.88
Pgp-inhibitor:	0.057	Pgp-substrate:	0.111
PAMPA:	0.381 ? 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):	0.059
20% Bioavailability (F20%):	0.412	30% Bioavailability (F30%):	0.478
50% Bioavailability (F50%):	0.784

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.68	MRP1:	0.974
Plasma Protein Binding (PPB):	90.05%	Volume Distribution (VD):	-0.203
Fu:	8.05% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.006
OATP1B3 inhibitor:	0.083	BCRP inhibitor:	0.027
BSEP inhibitor:	0.728

ADMET: Metabolism

CYP1A2-inhibitor:	0.008	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.992	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.823	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.067	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.812	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.817	CYP2C8-inhibitor:	0.061
HLM stability:	0.173 ? 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):

15.721

Half-life (T1/2):

1.828

ADMET: Toxicity

hERG Blockers:	0.131	hERG Blockers (10um):	0.594
Human Hepatotoxicity (H-HT):	0.672	Drug-induced Liver Injury (DILI):	0.243
AMES Toxicity:	0.29	Rat Oral Acute Toxicity:	0.263
Maximum Recommended Daily Dose:	0.788	Skin Sensitization:	0.02
Carcinogencity:	0.499	Eye Corrosion:	0.0
Eye Irritation:	0.143	Respiratory Toxicity:	0.371
Drug-induced Neurotoxicity:	0.566	Ototoxicity:	0.852
Hematotoxicity:	0.176	Drug-induced Nephrotoxicity:	0.093
Genotoxicity:	0.051	RPMI-8226 Immunitoxicity:	0.054
A549 Cytotoxicity:	0.126	Hek293 Cytotoxicity:	0.379
BCF:	0.756 ? 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:	3.64 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.36 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.385 ? 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
NPO21027	Daphnia magna	Species	Daphniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[20117838]
NPO21027	Daphnia magna	Species	Daphniidae	Eukaryota	n.a.	n.a.	n.a.	Database[Article]
NPO21027	Daphnia magna	Species	Daphniidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21027	Daphnia magna	Species	Daphniidae	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

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 NPC318475 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	17057
0.1-0.2	28683
0.2-0.3	3957
0.3-0.4	106
0.4-0.5	27
0.5-0.6	19
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	Natural Product ID
0.72	Intermediate Similarity	NPC227064
0.72	Intermediate Similarity	NPC329043
0.72	Intermediate Similarity	NPC58841
0.72	Intermediate Similarity	NPC161423
0.6731	Remote Similarity	NPC327115
0.6538	Remote Similarity	NPC214043
0.6538	Remote Similarity	NPC85774
0.6111	Remote Similarity	NPC144258
0.6078	Remote Similarity	NPC139397
0.6	Remote Similarity	NPC237712
0.5962	Remote Similarity	NPC307176
0.5962	Remote Similarity	NPC321874
0.5849	Remote Similarity	NPC2634
0.5849	Remote Similarity	NPC265782
0.5849	Remote Similarity	NPC251929
0.5789	Remote Similarity	NPC310010
0.5789	Remote Similarity	NPC119416
0.5789	Remote Similarity	NPC326627
0.5636	Remote Similarity	NPC282593
0.5536	Remote Similarity	NPC35734
0.5536	Remote Similarity	NPC159577
0.5536	Remote Similarity	NPC115023
0.5536	Remote Similarity	NPC602429
0.5439	Remote Similarity	NPC149203
0.5345	Remote Similarity	NPC249312
0.5345	Remote Similarity	NPC323765
0.5263	Remote Similarity	NPC257176
0.5172	Remote Similarity	NPC328539
0.5156	Remote Similarity	NPC111015

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC318475 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6433
0.1-0.2	2437
0.2-0.3	186
0.3-0.4	55
0.4-0.5	26
0.5-0.6	10
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	Drug ID	Developmental Stage
0.72	Intermediate Similarity	NPD3666	Phase 4
0.6226	Remote Similarity	NPD4221	Phase 4
0.5962	Remote Similarity	NPD4747	Phase 4
0.5893	Remote Similarity	NPD4693	Phase 3
0.5849	Remote Similarity	NPD4691	Approved
0.5789	Remote Similarity	NPD4753	Phase 2
0.5574	Remote Similarity	NPD6083	Phase 4
0.5574	Remote Similarity	NPD6084	Phase 2
0.5263	Remote Similarity	NPD3618	Phase 1
0.5254	Remote Similarity	NPD5330	Phase 4
0.5167	Remote Similarity	NPD5737	Phase 4
0.5082	Remote Similarity	NPD6409	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