NPASS Compound

Natural Product: NPC94751

Natural Product ID	NPC94751
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(15S)-16-Hydroxyabieta-8,11,13-Trien-19-Oic Acid
IUPAC Name	(1S,4aS,10aR)-7-[(2S)-1-hydroxypropan-2-yl]-1,4a-dimethyl-2,3,4,9,10,10a-hexahydrophenanthrene-1-carboxylic acid
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2431468
PubChem CID	72705062
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids

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 51 53 0 0 0 0 0 0 0 0999 V2000 -5.1021 0.8420 1.4646 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2636 0.7469 0.0945 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5665 -0.4993 -0.3923 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1182 -0.4467 -0.0735 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5290 -1.3680 0.7597 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1866 -1.3500 1.0781 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4121 -0.3506 0.5236 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9416 0.6032 -0.3188 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3034 0.5351 -0.6046 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2015 1.7113 -0.9581 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2934 1.5997 -0.7430 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6897 0.1497 -0.4733 C 0 0 2 0 0 0 0 0 0 0 0 0 1.0531 -0.2512 0.8119 C 0 0 1 0 0 0 0 0 0 0 0 0 1.1678 0.8931 1.8025 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6178 -1.4700 1.4505 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0833 -1.6602 1.2931 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8342 -0.5636 0.6305 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1278 -0.0982 -0.6108 C 0 0 1 0 0 0 0 0 0 0 0 0 3.4056 -1.1680 -1.6787 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8126 1.1365 -1.0799 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4579 1.1853 -2.1710 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7988 2.3300 -0.3601 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8144 -0.7446 -1.8628 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7402 1.7069 1.7660 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3662 0.5810 -0.0866 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9868 1.6474 -0.4536 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9907 -1.3675 0.1507 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1359 -2.1502 1.1934 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7496 -2.1010 1.7497 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7889 1.2575 -1.2636 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3694 1.6580 -2.0521 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5873 2.6926 -0.6097 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8152 2.0171 -1.6242 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5212 2.2635 0.1155 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1528 -0.4234 -1.2890 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0179 0.4266 2.8220 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3274 1.6089 1.7068 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1392 1.3757 1.8381 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3886 -1.4559 2.5383 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1281 -2.4214 1.0873 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3219 -2.6267 0.7563 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5879 -1.8194 2.2949 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8123 -1.0128 0.2741 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1675 0.2496 1.3027 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6055 -1.1138 -2.4191 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5320 -2.1696 -1.2194 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3784 -0.9247 -2.1900 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6459 2.8901 -0.2824 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9170 -0.6456 -2.0147 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5829 -1.8234 -2.0523 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2301 -0.0816 -2.5151 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 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 1 13 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 6 18 20 1 0 20 21 2 0 20 22 1 0 3 23 1 0 9 4 1 0 18 12 1 0 13 7 1 0 1 24 1 0 2 25 1 0 2 26 1 0 3 27 1 1 5 28 1 0 6 29 1 0 9 30 1 0 10 31 1 0 10 32 1 0 11 33 1 0 11 34 1 0 12 35 1 6 14 36 1 0 14 37 1 0 14 38 1 0 15 39 1 0 15 40 1 0 16 41 1 0 16 42 1 0 17 43 1 0 17 44 1 0 19 45 1 0 19 46 1 0 19 47 1 0 22 48 1 0 23 49 1 0 23 50 1 0 23 51 1 0 M END

Standard InCHIKey	GOADHRDZJUNBQS-HSGBFHSBSA-N
Standard InCHI	InChI=1S/C20H28O3/c1-13(12-21)14-5-7-16-15(11-14)6-8-17-19(16,2)9-4-10-20(17,3)18(22)23/h5,7,11,13,17,21H,4,6,8-10,12H2,1-3H3,(H,22,23)/t13-,17-,19-,20+/m1/s1
SMILES	OC[C@H](c1ccc2c(c1)CC[C@@H]1[C@]2(C)CCC[C@]1(C)C(=O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	316.2	Volume:	344.632 ? Van der Waals volume.
Dense:	0.918	LogP:	3.35 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.899 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.744 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	17.0
TPSA:	57.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.89	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.748	Fsp³:	0.65
MCE-18:	73.182 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.049	Fluc inhibitor:	0.017 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.05 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.021 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.161	Promiscuous compounds:	0.033

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.143	MDCK Permeability:	-4.769
Pgp-inhibitor:	0.008	Pgp-substrate:	0.033
PAMPA:	0.973 ? 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%):	0.012	30% Bioavailability (F30%):	0.01
50% Bioavailability (F50%):	0.145

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.009	MRP1:	0.976
Plasma Protein Binding (PPB):	93.282%	Volume Distribution (VD):	-0.226
Fu:	4.977% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.846
OATP1B3 inhibitor:	0.753	BCRP inhibitor:	0.033
BSEP inhibitor:	0.894

ADMET: Metabolism

CYP1A2-inhibitor:	0.284	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.079	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.966	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.013	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.839	CYP3A4-substrate:	0.58
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.123
HLM stability:	0.03 ? 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):

2.795

Half-life (T1/2):

1.164

ADMET: Toxicity

hERG Blockers:	0.053	hERG Blockers (10um):	0.023
Human Hepatotoxicity (H-HT):	0.832	Drug-induced Liver Injury (DILI):	0.74
AMES Toxicity:	0.168	Rat Oral Acute Toxicity:	0.125
Maximum Recommended Daily Dose:	0.462	Skin Sensitization:	0.978
Carcinogencity:	0.807	Eye Corrosion:	0.025
Eye Irritation:	0.908	Respiratory Toxicity:	0.814
Drug-induced Neurotoxicity:	0.02	Ototoxicity:	0.818
Hematotoxicity:	0.654	Drug-induced Nephrotoxicity:	0.966
Genotoxicity:	0.747	RPMI-8226 Immunitoxicity:	0.026
A549 Cytotoxicity:	0.059	Hek293 Cytotoxicity:	0.087
BCF:	0.956 ? 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:	3.856 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.445 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.706 ? 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
NPO14738	Illicium majus	Species	Schisandraceae	Eukaryota	Roots	n.a.	n.a.	PMID[24070022]
NPO14738	Illicium majus	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14738	Illicium majus	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14738	Illicium majus	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]

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
IC50	1
TC50	1

Activity Type	# Activity
Cell line	1
Organism	1

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
NPT189	Cell line	Vero	Chlorocebus aethiops	TC50	=	138.7	uM/ml	PMID[19124248]
NPT3119	Organism	Human coxsackievirus B3	Human coxsackievirus B3	IC50	=	17400000.0	nM	PMID[16309311]

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 NPC94751 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	18366
0.1-0.2	30233
0.2-0.3	1152
0.3-0.4	63
0.4-0.5	15
0.5-0.6	10
0.6-0.7	9
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC142326
0.8269	Intermediate Similarity	NPC128248
0.8269	Intermediate Similarity	NPC136810
0.7368	Intermediate Similarity	NPC212891
0.7368	Intermediate Similarity	NPC480861
0.7321	Intermediate Similarity	NPC95126
0.6842	Remote Similarity	NPC133809
0.65	Remote Similarity	NPC221275
0.6441	Remote Similarity	NPC162935
0.6441	Remote Similarity	NPC249340
0.6379	Remote Similarity	NPC42657
0.629	Remote Similarity	NPC45794
0.6129	Remote Similarity	NPC480862
0.6129	Remote Similarity	NPC480860
0.6	Remote Similarity	NPC480867
0.5968	Remote Similarity	NPC603947
0.5968	Remote Similarity	NPC608624
0.5806	Remote Similarity	NPC234337
0.5806	Remote Similarity	NPC133389
0.5397	Remote Similarity	NPC93287
0.5362	Remote Similarity	NPC480863
0.5238	Remote Similarity	NPC225079
0.5238	Remote Similarity	NPC471186
0.5077	Remote Similarity	NPC471189
0.5072	Remote Similarity	NPC480866

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC94751 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3195
0.1-0.2	5718
0.2-0.3	235
0.3-0.4	1
0.4-0.5	0
0.5-0.6	0
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
0.6066	Remote Similarity	NPD4199	Phase 3

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