NPASS Compound

Natural Product: NPC491678

Natural Product ID	NPC491678
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(10~{R},13~{S},16~{S},17~{R})-17-[(1~{S},2~{R},5~{S})-2,6-dihydroxy-1,5-dimethyl-hexyl]-16-hydroxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
IUPAC Name	(10~{R},13~{S},16~{S},17~{R})-17-[(1~{S},2~{R},5~{S})-2,6-dihydroxy-1,5-dimethyl-hexyl]-16-hydroxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
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 75 78 0 0 0 0 0 0 0 0999 V2000 6.8338 0.0315 -1.0260 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4566 -1.0270 -0.0300 C 0 0 2 0 0 0 0 0 0 0 0 0 7.0507 -2.3699 -0.3466 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6444 -2.8470 -1.5904 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9583 -1.1427 0.0127 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3318 0.1853 0.4274 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8145 -0.0762 0.4293 C 0 0 1 0 0 0 0 0 0 0 0 0 2.6763 -1.1077 1.3705 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1754 1.1524 1.1059 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5853 2.3100 0.2624 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7479 0.9774 1.4255 C 0 0 1 0 0 0 0 0 0 0 0 0 0.1861 2.1666 2.1769 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8453 3.3452 2.0299 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2933 2.2439 1.8515 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5042 0.9376 1.1790 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7911 0.7000 0.5461 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5436 1.8844 0.0086 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5450 1.4259 -1.0626 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0429 0.0579 -0.7606 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3380 -0.2481 -0.6784 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7251 -1.6346 -0.3737 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8892 -1.9793 -0.6983 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8043 -2.5979 0.2839 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5716 -1.7730 0.6999 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1010 -1.0761 -0.5261 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.0873 -1.9850 -1.7463 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7464 -0.4410 -0.4431 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6514 -1.3371 0.0308 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3233 -0.6091 -0.2500 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2382 0.7549 0.3261 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.2093 1.8347 -0.7361 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0297 0.9990 -0.5239 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7088 -0.3275 -1.6119 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0004 0.1455 -1.7531 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7888 -0.7621 1.0023 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7041 -3.0854 0.4192 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1613 -2.2777 -0.2769 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2801 -3.4972 -1.9679 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6053 -1.4314 -0.9984 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6558 -1.9567 0.7085 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6866 0.4264 1.4506 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5803 0.9255 -0.3281 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4803 -0.2742 -0.5607 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9044 -0.6972 2.2451 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7039 1.2221 2.0692 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9700 1.9679 -0.7563 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9103 3.1462 0.1600 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5334 2.7426 0.7077 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6640 0.1099 2.1096 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2758 1.9358 3.3031 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6577 3.9299 2.7788 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8787 2.1861 2.8226 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5987 3.1425 1.3194 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3497 0.1533 1.9894 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4895 0.3061 1.3584 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9518 2.6858 -0.4160 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1946 2.3691 0.7973 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4235 2.1012 -1.0680 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0640 1.4932 -2.0622 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0404 0.5413 -0.8405 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5079 -3.4273 -0.3837 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2821 -2.9291 1.2183 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8242 -2.4489 1.1530 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0008 -1.0520 1.4412 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0794 -2.2641 -2.0949 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6317 -1.3602 -2.5691 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4746 -2.8626 -1.5105 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5088 -0.1393 -1.4811 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7299 -1.6481 1.0752 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6144 -2.2580 -0.5961 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4294 -1.3267 0.0719 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2349 -0.5529 -1.3656 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3944 2.8024 -0.2413 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0418 1.7254 -1.4622 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6843 1.7654 -1.3536 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 2 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 7 9 1 0 9 10 1 0 9 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 0 17 18 1 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 21 23 1 0 23 24 1 0 24 25 1 0 25 26 1 6 25 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 6 30 11 1 0 30 15 1 0 27 16 1 0 25 19 1 0 1 32 1 0 1 33 1 0 1 34 1 0 2 35 1 1 3 36 1 0 3 37 1 0 4 38 1 0 5 39 1 0 5 40 1 0 6 41 1 0 6 42 1 0 7 43 1 6 8 44 1 0 9 45 1 1 10 46 1 0 10 47 1 0 10 48 1 0 11 49 1 1 12 50 1 1 13 51 1 0 14 52 1 0 14 53 1 0 15 54 1 0 16 55 1 0 17 56 1 0 17 57 1 0 18 58 1 0 18 59 1 0 20 60 1 0 23 61 1 0 23 62 1 0 24 63 1 0 24 64 1 0 26 65 1 0 26 66 1 0 26 67 1 0 27 68 1 0 28 69 1 0 28 70 1 0 29 71 1 0 29 72 1 0 31 73 1 0 31 74 1 0 31 75 1 0 M END

Standard InCHIKey	WTHGALCYJGSRNA-GGAUMGTOSA-N
Standard InCHI	InChI=1S/C27H44O4/c1-16(15-28)5-8-23(30)17(2)25-24(31)14-22-20-7-6-18-13-19(29)9-11-26(18,3)21(20)10-12-27(22,25)4/h13,16-17,20-25,28,30-31H,5-12,14-15H2,1-4H3/t16-,17+,20?,21?,22?,23+,24-,25-,26-,27-/m0/s1
SMILES	C[C@H](CO)CC[C@@H](O)[C@@H](C)[C@H]1[C@@H](O)CC2C3CCC4=CC(=O)CC[C@]4(C)C3CC[C@@]21C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	432.32	Volume:	471.21 ? Van der Waals volume.
Dense:	0.917	LogP:	2.94 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.019 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.108 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	21.0
TPSA:	77.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.577	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.76	Fsp³:	0.889
MCE-18:	71.373 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.687	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.018 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.004 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.242	Promiscuous compounds:	0.278

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.283	MDCK Permeability:	-5.006
Pgp-inhibitor:	0.334	Pgp-substrate:	0.48
PAMPA:	0.941 ? 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%):	0.084	30% Bioavailability (F30%):	0.164
50% Bioavailability (F50%):	0.973

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.004	MRP1:	0.433
Plasma Protein Binding (PPB):	84.273%	Volume Distribution (VD):	-0.507
Fu:	12.128% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.827
OATP1B3 inhibitor:	0.05	BCRP inhibitor:	0.186
BSEP inhibitor:	0.99

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.844	CYP2C19-substrate:	0.003
CYP2C9-inhibitor:	0.021	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.095	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.969	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.861
HLM stability:	0.633 ? 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):

15.022

Half-life (T1/2):

1.894

ADMET: Toxicity

hERG Blockers:	0.106	hERG Blockers (10um):	0.406
Human Hepatotoxicity (H-HT):	0.599	Drug-induced Liver Injury (DILI):	0.102
AMES Toxicity:	0.192	Rat Oral Acute Toxicity:	0.113
Maximum Recommended Daily Dose:	0.613	Skin Sensitization:	0.76
Carcinogencity:	0.564	Eye Corrosion:	0.003
Eye Irritation:	0.229	Respiratory Toxicity:	0.299
Drug-induced Neurotoxicity:	0.238	Ototoxicity:	0.854
Hematotoxicity:	0.178	Drug-induced Nephrotoxicity:	0.314
Genotoxicity:	0.025	RPMI-8226 Immunitoxicity:	0.068
A549 Cytotoxicity:	0.159	Hek293 Cytotoxicity:	0.393
BCF:	0.544 ? 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:	3.321 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.99 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.013 ? 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
NPO55537	Tribulus species	Genus	Muricidae	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 NPC491678 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	18036
0.1-0.2	28315
0.2-0.3	3322
0.3-0.4	132
0.4-0.5	29
0.5-0.6	21
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	Natural Product ID
0.7541	Intermediate Similarity	NPC111015
0.6	Remote Similarity	NPC214043
0.6	Remote Similarity	NPC85774
0.5938	Remote Similarity	NPC1272
0.5938	Remote Similarity	NPC470614
0.5806	Remote Similarity	NPC237712
0.5738	Remote Similarity	NPC227064
0.5738	Remote Similarity	NPC329043
0.5738	Remote Similarity	NPC58841
0.5738	Remote Similarity	NPC161423
0.5645	Remote Similarity	NPC327115
0.55	Remote Similarity	NPC307176
0.55	Remote Similarity	NPC321874
0.5397	Remote Similarity	NPC144258
0.5238	Remote Similarity	NPC282593
0.5156	Remote Similarity	NPC35734
0.5156	Remote Similarity	NPC159577
0.5156	Remote Similarity	NPC115023
0.5156	Remote Similarity	NPC602429
0.5152	Remote Similarity	NPC310010
0.5152	Remote Similarity	NPC326627
0.5122	Remote Similarity	NPC260665
0.5082	Remote Similarity	NPC139397
0.5077	Remote Similarity	NPC149203

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC491678 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6896
0.1-0.2	1997
0.2-0.3	190
0.3-0.4	38
0.4-0.5	24
0.5-0.6	4
0.6-0.7	0
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
0.5738	Remote Similarity	NPD3666	Phase 4
0.55	Remote Similarity	NPD4747	Phase 4
0.5238	Remote Similarity	NPD4221	Phase 4
0.5152	Remote Similarity	NPD4753	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