NPASS Compound

Natural Product: NPC72232

Natural Product ID	NPC72232
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	HIGFJBWLJMUGFT-XTNBKHNLSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	13990469
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0003566] Cholestane steroids [CHEMONTID:0001469] Cholesterols 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 67 70 0 0 0 0 0 0 0 0999 V2000 6.4650 -0.4688 -0.6214 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2236 0.9767 -0.4151 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6640 1.2981 1.0133 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8993 1.5344 -0.7362 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6957 1.0556 -0.0078 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4116 -0.3751 -0.1445 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1238 -0.8107 0.5809 C 0 0 1 0 0 0 0 0 0 0 0 0 2.1812 -0.5382 2.0308 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9803 -0.3193 -0.1875 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0518 -0.9357 -1.5947 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3998 -1.2215 -1.9953 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1315 -0.3923 -1.0397 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5539 -0.5617 -0.7983 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.4407 -0.6911 -1.9942 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8278 -1.0671 -1.4490 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2567 -0.0756 -0.4214 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6256 -0.0544 -0.1263 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1172 0.8302 0.8081 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2644 1.6801 1.4394 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8961 1.6489 1.1350 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3886 0.7789 0.2115 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9754 0.7496 -0.0997 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0255 1.0661 0.9983 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9974 0.0655 1.3410 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3846 -0.7341 0.2673 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.5489 -2.1958 0.5259 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4990 0.8409 1.0959 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8357 -0.9377 -1.3811 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5748 -1.0681 0.3292 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5225 -0.5674 -1.0567 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9696 1.5539 -1.0575 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7486 1.0310 1.0531 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5747 2.3646 1.2149 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1602 0.6479 1.7534 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7362 1.4348 -1.8513 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9514 2.6576 -0.5144 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8176 1.4045 1.0489 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7964 1.6320 -0.3977 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3934 -0.6747 -1.2019 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2705 -0.9408 0.3261 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1666 -1.9375 0.4677 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3886 -1.0970 2.5426 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1494 -0.9576 2.4157 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1827 0.5223 2.3170 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9829 0.7722 -0.2640 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4168 -0.1473 -2.2845 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6563 -1.8452 -1.5987 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5701 -2.2932 -1.9713 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5561 -0.9040 -3.0668 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8475 0.6806 -1.2284 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8530 -1.3508 -0.0799 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1451 -1.4931 -2.6948 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5756 0.2941 -2.4856 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6784 -2.0308 -0.9185 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5028 -1.1286 -2.3013 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3116 -0.7446 -0.6404 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6687 2.3676 2.1700 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3075 2.3646 1.6902 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8120 1.5200 -0.9158 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5108 2.0596 0.8303 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6293 1.2591 1.9352 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4242 -0.6232 2.1317 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1798 0.6043 1.9082 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3223 -2.6862 -0.1189 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3411 -2.8129 0.4487 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9408 -2.3439 1.5758 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1635 1.3305 0.5177 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 7 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 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 1 18 27 1 0 25 9 1 0 25 12 1 0 22 13 1 0 21 16 1 0 1 28 1 0 1 29 1 0 1 30 1 0 2 31 1 0 3 32 1 0 3 33 1 0 3 34 1 0 4 35 1 0 4 36 1 0 5 37 1 0 5 38 1 0 6 39 1 0 6 40 1 0 7 41 1 1 8 42 1 0 8 43 1 0 8 44 1 0 9 45 1 6 10 46 1 0 10 47 1 0 11 48 1 0 11 49 1 0 12 50 1 6 13 51 1 1 14 52 1 0 14 53 1 0 15 54 1 0 15 55 1 0 17 56 1 0 19 57 1 0 20 58 1 0 22 59 1 6 23 60 1 0 23 61 1 0 24 62 1 0 24 63 1 0 26 64 1 0 26 65 1 0 26 66 1 0 27 67 1 0 M END

Standard InCHIKey	HIGFJBWLJMUGFT-XTNBKHNLSA-N
Standard InCHI	InChI=1S/C26H40O/c1-17(2)6-5-7-18(3)24-12-13-25-23-10-8-19-16-20(27)9-11-21(19)22(23)14-15-26(24,25)4/h9,11,16-18,22-25,27H,5-8,10,12-15H2,1-4H3/t18-,22-,23-,24-,25+,26-/m1/s1
SMILES	CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CCc4cc(ccc4[C@H]3CC[C@]12C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	368.31	Volume:	424.907 ? Van der Waals volume.
Dense:	0.867	LogP:	7.931 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	5.218 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-7.19 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	20.0
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:	0.577	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.787	Fsp³:	0.769
MCE-18:	83.478 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.766	Fluc inhibitor:	0.609 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.017 ? 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:	0.415	Promiscuous compounds:	0.095

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.14	MDCK Permeability:	-4.988
Pgp-inhibitor:	0.0	Pgp-substrate:	0.035
PAMPA:	0.01 ? 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):	0.0
20% Bioavailability (F20%):	0.024	30% Bioavailability (F30%):	0.732
50% Bioavailability (F50%):	0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.675	MRP1:	0.145
Plasma Protein Binding (PPB):	96.142%	Volume Distribution (VD):	0.284
Fu:	3.98% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.056
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.691	CYP1A2-substrate:	0.988
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.902
CYP2C9-inhibitor:	0.501	CYP2C9-substrate:	0.543
CYP2D6-inhibitor:	0.162	CYP2D6-substrate:	0.934
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.807	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

9.699

Half-life (T1/2):

0.47

ADMET: Toxicity

hERG Blockers:	0.278	hERG Blockers (10um):	0.693
Human Hepatotoxicity (H-HT):	0.66	Drug-induced Liver Injury (DILI):	0.109
AMES Toxicity:	0.379	Rat Oral Acute Toxicity:	0.243
Maximum Recommended Daily Dose:	0.62	Skin Sensitization:	0.844
Carcinogencity:	0.789	Eye Corrosion:	0.33
Eye Irritation:	0.954	Respiratory Toxicity:	0.836
Drug-induced Neurotoxicity:	0.098	Ototoxicity:	0.417
Hematotoxicity:	0.277	Drug-induced Nephrotoxicity:	0.159
Genotoxicity:	0.02	RPMI-8226 Immunitoxicity:	0.054
A549 Cytotoxicity:	0.514	Hek293 Cytotoxicity:	0.643
BCF:	3.121 ? 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:	5.545 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.992 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.347 ? 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
NPO14183	Dendronephthya studeri	Species	Nephtheidae	Eukaryota	n.a.	at a depth of 20 m, the coast of Xiaodong Sea, Hainan Province, China	2001-DEC	PMID[21192715]
NPO14183	Dendronephthya studeri	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	PMID[21192715]
NPO14183	Dendronephthya studeri	Species	Nephtheidae	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 NPC72232 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	22403
0.1-0.2	26246
0.2-0.3	1153
0.3-0.4	27
0.4-0.5	16
0.5-0.6	8
0.6-0.7	6
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	Natural Product ID
0.6667	Remote Similarity	NPC322753
0.6066	Remote Similarity	NPC190501
0.6066	Remote Similarity	NPC48342
0.6066	Remote Similarity	NPC318552
0.6066	Remote Similarity	NPC329477
0.6066	Remote Similarity	NPC164649
0.5938	Remote Similarity	NPC79933
0.5806	Remote Similarity	NPC77569
0.5806	Remote Similarity	NPC142198
0.5806	Remote Similarity	NPC324264
0.5781	Remote Similarity	NPC99734
0.5625	Remote Similarity	NPC137496
0.5538	Remote Similarity	NPC30491
0.5538	Remote Similarity	NPC262936

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC72232 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5669
0.1-0.2	3344
0.2-0.3	102
0.3-0.4	23
0.4-0.5	4
0.5-0.6	6
0.6-0.7	2
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
0.6066	Remote Similarity	NPD3019	Phase 4
0.6066	Remote Similarity	NPD3091	Phase 4
0.5806	Remote Similarity	NPD3092	Phase 4
0.5781	Remote Similarity	NPD4059	Phase 4
0.5397	Remote Similarity	NPD3094	Phase 4
0.5373	Remote Similarity	NPD3638	Discontinued
0.5278	Remote Similarity	NPD5736	Phase 4
0.527	Remote Similarity	NPD6663	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