NPASS Compound

Natural Product: NPC589117

Natural Product ID	NPC589117
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(5~{S},8~{S},9~{S},10~{S},13~{R},14~{S},17~{R})-17-[(1~{R},4~{R})-4-ethyl-1,5-dimethyl-hexyl]-10,13-dimethyl-1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-one
IUPAC Name	(5~{S},8~{S},9~{S},10~{S},13~{R},14~{S},17~{R})-17-[(1~{R},4~{R})-4-ethyl-1,5-dimethyl-hexyl]-10,13-dimethyl-1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[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 80 83 0 0 0 0 0 0 0 0999 V2000 -7.1793 -0.8383 -0.6504 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7674 -0.1948 -0.8726 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3920 0.5737 0.3467 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.1389 1.2868 0.3814 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7853 0.7473 0.2788 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3205 0.0357 -0.9341 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4287 0.9397 -2.1414 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0094 -0.6562 -0.8142 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7397 -1.3201 -2.1647 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6851 -0.8664 -2.5313 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2319 -0.8804 -1.1323 C 0 0 1 0 0 0 0 0 0 0 0 0 2.6517 -0.7164 -0.9362 C 0 0 1 0 0 0 0 0 0 0 0 0 3.3905 0.0157 -2.0245 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8682 0.0836 -1.8032 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2937 -0.2338 -0.4164 C 0 0 1 0 0 0 0 0 0 0 0 0 6.7277 0.1206 -0.1561 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1007 -0.6055 1.0835 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2454 -0.8376 1.3406 O 0 0 0 0 0 0 0 0 0 0 0 0 5.9951 -1.0236 1.9764 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9289 0.0559 1.9875 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3545 0.3384 0.6148 C 0 0 1 0 0 0 0 0 0 0 0 0 4.2330 1.8320 0.5163 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0564 -0.4103 0.4639 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0150 0.2528 1.3097 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6153 -0.2606 1.0521 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2279 0.0108 -0.4210 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3794 1.4554 -0.6243 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7231 -0.2185 1.6114 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3263 0.6120 2.7880 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1460 -1.5894 1.6057 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7717 -0.0208 -0.1904 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0948 -1.6828 0.0470 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5299 -1.1072 -1.6480 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9573 0.5461 -1.6941 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1128 -0.9666 -1.2323 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2084 1.3900 0.3835 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1884 2.0750 1.2431 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2035 2.0532 -0.4980 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4590 0.2237 1.2258 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1162 1.6846 0.3526 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0145 -0.8003 -1.1277 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3859 0.7262 -2.7142 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6458 0.8556 -2.8790 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6080 1.9739 -1.7648 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1712 -1.5149 -0.0899 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4745 -1.1350 -2.9258 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6439 -2.4282 -2.0675 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1723 -1.5621 -3.2130 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7043 0.1464 -2.9268 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9336 -1.9159 -0.7468 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0862 -1.7780 -1.1136 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2505 -0.5951 -2.9735 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0492 0.9961 -2.3012 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2854 1.1039 -2.0521 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4448 -0.6032 -2.4899 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2140 -1.3556 -0.3010 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3181 -0.2178 -1.0341 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9115 1.1908 0.0368 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3212 -1.1586 3.0112 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5396 -1.9960 1.6530 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1517 -0.3020 2.6924 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3926 0.9547 2.4470 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2687 2.2858 0.4935 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7270 2.2222 -0.3568 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7749 2.2711 1.4244 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2607 -1.3864 1.0209 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1863 0.0820 2.3919 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9889 1.3547 1.2000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0398 0.2188 1.7650 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5550 -1.3570 1.1780 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2703 1.9683 -1.3214 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2002 1.9692 0.3732 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4548 1.7010 -0.7921 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8255 -0.3165 1.6196 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2089 0.7812 2.8183 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5430 0.1071 3.7649 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8686 1.5784 2.8382 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2678 -1.6499 2.3149 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7804 -1.9389 0.6272 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8450 -2.3798 1.9731 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 1 0 6 7 1 0 6 8 1 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 2 0 17 19 1 0 19 20 1 0 20 21 1 0 21 22 1 6 21 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 6 3 28 1 0 28 29 1 0 28 30 1 0 26 8 1 0 26 11 1 0 23 12 1 0 21 15 1 0 1 31 1 0 1 32 1 0 1 33 1 0 2 34 1 0 2 35 1 0 3 36 1 1 4 37 1 0 4 38 1 0 5 39 1 0 5 40 1 0 6 41 1 6 7 42 1 0 7 43 1 0 7 44 1 0 8 45 1 1 9 46 1 0 9 47 1 0 10 48 1 0 10 49 1 0 11 50 1 1 12 51 1 6 13 52 1 0 13 53 1 0 14 54 1 0 14 55 1 0 15 56 1 6 16 57 1 0 16 58 1 0 19 59 1 0 19 60 1 0 20 61 1 0 20 62 1 0 22 63 1 0 22 64 1 0 22 65 1 0 23 66 1 1 24 67 1 0 24 68 1 0 25 69 1 0 25 70 1 0 27 71 1 0 27 72 1 0 27 73 1 0 28 74 1 0 29 75 1 0 29 76 1 0 29 77 1 0 30 78 1 0 30 79 1 0 30 80 1 0 M END

Standard InCHIKey	BVVFRHKBULZQCQ-MJLZOCCMSA-N
Standard InCHI	InChI=1S/C29H50O/c1-7-21(19(2)3)9-8-20(4)25-12-13-26-24-11-10-22-18-23(30)14-16-28(22,5)27(24)15-17-29(25,26)6/h19-22,24-27H,7-18H2,1-6H3/t20-,21-,22+,24-,25-,26+,27+,28+,29-/m1/s1
SMILES	CC[C@H](CC[C@@H](C)[C@H]1CC[C@H]2[C@H]3CC[C@H]4CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C)C(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	414.39	Volume:	482.068 ? Van der Waals volume.
Dense:	0.86	LogP:	8.526 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	5.412 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-8.312 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	21.0
TPSA:	17.07 ? Topological Polar Surface Area.	H-Bond Acceptor:	1.0
H-Bond Donor:	0.0	Rings:	4.0
Heavy Atoms:	1.0

MedChem Properties

QED Drug-Likeness Score:	0.427	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.355	Fsp³:	0.966
MCE-18:	69.158 ? 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:	0.711	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.009 ? 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:	0.802	Promiscuous compounds:	0.261

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.032	MDCK Permeability:	-4.995
Pgp-inhibitor:	0.001	Pgp-substrate:	0.001
PAMPA:	0.021 ? 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%):	0.006	30% Bioavailability (F30%):	0.182
50% Bioavailability (F50%):	0.974

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.015	MRP1:	0.007
Plasma Protein Binding (PPB):	92.834%	Volume Distribution (VD):	0.05
Fu:	9.426% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.218
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.028	CYP1A2-substrate:	0.866
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.934
CYP2C9-inhibitor:	0.003	CYP2C9-substrate:	0.092
CYP2D6-inhibitor:	0.181	CYP2D6-substrate:	0.498
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	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):

15.956

Half-life (T1/2):

0.442

ADMET: Toxicity

hERG Blockers:	0.267	hERG Blockers (10um):	0.453
Human Hepatotoxicity (H-HT):	0.686	Drug-induced Liver Injury (DILI):	0.445
AMES Toxicity:	0.171	Rat Oral Acute Toxicity:	0.068
Maximum Recommended Daily Dose:	0.442	Skin Sensitization:	0.989
Carcinogencity:	0.882	Eye Corrosion:	0.926
Eye Irritation:	0.995	Respiratory Toxicity:	0.966
Drug-induced Neurotoxicity:	0.176	Ototoxicity:	0.376
Hematotoxicity:	0.69	Drug-induced Nephrotoxicity:	0.603
Genotoxicity:	0.001	RPMI-8226 Immunitoxicity:	0.038
A549 Cytotoxicity:	0.518	Hek293 Cytotoxicity:	0.661
BCF:	3.243 ? 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:	4.985 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.225 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.874 ? 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
NPO59482	Larix kaempferi (Lamb.) Carr	Genus	Pinaceae	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 NPC589117 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	27703
0.1-0.2	20765
0.2-0.3	1233
0.3-0.4	126
0.4-0.5	21
0.5-0.6	7
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
0.7556	Intermediate Similarity	NPC184819
0.6667	Remote Similarity	NPC143597
0.6667	Remote Similarity	NPC151464
0.5833	Remote Similarity	NPC288296
0.5833	Remote Similarity	NPC53245
0.5686	Remote Similarity	NPC148174
0.5385	Remote Similarity	NPC324607
0.5385	Remote Similarity	NPC321732
0.5357	Remote Similarity	NPC20610
0.5179	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 NPC589117 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7313
0.1-0.2	1721
0.2-0.3	90
0.3-0.4	22
0.4-0.5	2
0.5-0.6	1
0.6-0.7	1
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
0.6327	Remote Similarity	NPD4789	Approved
0.5385	Remote Similarity	NPD3698	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