NPASS Compound

Natural Product: NPC471035

Natural Product ID	NPC471035
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	WQBNGXOJBVBQKP-JKAPWZSASA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2337572
PubChem CID	5459043
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0003782] Kaurane 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 54 0 0 0 0 0 0 0 0999 V2000 -0.4135 -1.6207 1.6275 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6159 -0.7861 0.3501 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3049 -1.7707 -0.5977 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7589 -1.8497 -0.2845 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3921 -0.5494 -0.6472 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6348 0.6595 -0.2143 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4088 0.4177 0.6022 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6080 1.7274 0.5150 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6900 1.4940 1.2088 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5085 0.5717 0.3558 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7613 -0.5662 -0.2204 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6170 -1.8148 -0.0444 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9934 -1.5092 -0.6216 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6396 -0.3168 -0.0023 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7521 0.1759 1.1263 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5048 0.8273 -0.9603 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4196 1.2932 -1.7936 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1456 1.3237 -0.7815 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6587 2.2342 -1.5012 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6085 1.4595 0.6746 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3309 1.5584 -1.3566 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7170 2.7505 -1.4241 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5829 1.0870 -2.4223 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2371 -2.6755 1.3749 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3279 -1.2047 2.3018 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3917 -1.6123 2.1944 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8564 -2.7859 -0.4449 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1562 -1.5001 -1.6395 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1944 -2.6539 -0.9480 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9987 -2.1327 0.7390 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4486 -0.5246 -1.7761 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4518 -0.5687 -0.3205 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7286 0.3950 1.6885 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2168 2.5331 0.9701 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4501 1.9081 -0.5584 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5545 1.1766 2.2398 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2271 2.4806 1.2627 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6252 -0.4588 -1.3317 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6928 -2.1315 1.0054 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1894 -2.6311 -0.6396 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8753 -1.4039 -1.7067 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6396 -2.3894 -0.4319 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6765 -0.4773 0.3152 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1619 1.1019 1.5752 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5960 -0.5454 1.9154 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1667 2.1258 -2.4199 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4074 0.8618 -1.8605 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4178 1.2228 1.7509 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4662 2.5352 0.5605 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6472 1.1991 0.4734 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7932 1.3595 -3.3881 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 7 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 14 16 1 0 16 17 2 0 16 18 1 0 18 19 2 0 6 20 1 0 6 21 1 0 21 22 2 0 21 23 1 0 7 2 1 0 11 2 1 0 15 10 1 0 18 10 1 0 1 24 1 0 1 25 1 0 1 26 1 0 3 27 1 0 3 28 1 0 4 29 1 0 4 30 1 0 5 31 1 0 5 32 1 0 7 33 1 0 8 34 1 0 8 35 1 0 9 36 1 0 9 37 1 0 11 38 1 0 12 39 1 0 12 40 1 0 13 41 1 0 13 42 1 0 14 43 1 0 15 44 1 0 15 45 1 0 17 46 1 0 17 47 1 0 20 48 1 0 20 49 1 0 20 50 1 0 23 51 1 0 M END

Standard InCHIKey	WQBNGXOJBVBQKP-JKAPWZSASA-N
Standard InCHI	InChI=1S/C20H28O3/c1-12-13-5-6-15-18(2)8-4-9-19(3,17(22)23)14(18)7-10-20(15,11-13)16(12)21/h13-15H,1,4-11H2,2-3H3,(H,22,23)/t13-,14-,15-,18+,19-,20+/m0/s1
SMILES	CC12CCCC(C1CCC34C2CCC(C3)C(=C)C4=O)(C)C(=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	316.2	Volume:	338.712 ? Van der Waals volume.
Dense:	0.934	LogP:	2.898 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.838 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.837 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	22.0
TPSA:	54.37 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.737	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.466	Fsp³:	0.8
MCE-18:	102.0 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.033	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.008 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.085 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.683	Promiscuous compounds:	0.004

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.904	MDCK Permeability:	-4.754
Pgp-inhibitor:	0.025	Pgp-substrate:	0.0
PAMPA:	0.65 ? 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):	0.029
20% Bioavailability (F20%):	0.0	30% Bioavailability (F30%):	0.007
50% Bioavailability (F50%):	0.069

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.071	MRP1:	0.978
Plasma Protein Binding (PPB):	97.812%	Volume Distribution (VD):	-0.44
Fu:	2.591% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.193
OATP1B3 inhibitor:	0.993	BCRP inhibitor:	0.0
BSEP inhibitor:	0.883

ADMET: Metabolism

CYP1A2-inhibitor:	0.169	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.771	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.925	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.708	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.962	CYP2C8-inhibitor:	0.043
HLM stability:	0.083 ? 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):

1.943

Half-life (T1/2):

1.383

ADMET: Toxicity

hERG Blockers:	0.05	hERG Blockers (10um):	0.18
Human Hepatotoxicity (H-HT):	0.659	Drug-induced Liver Injury (DILI):	0.335
AMES Toxicity:	0.105	Rat Oral Acute Toxicity:	0.233
Maximum Recommended Daily Dose:	0.726	Skin Sensitization:	0.328
Carcinogencity:	0.404	Eye Corrosion:	0.006
Eye Irritation:	0.389	Respiratory Toxicity:	0.739
Drug-induced Neurotoxicity:	0.12	Ototoxicity:	0.854
Hematotoxicity:	0.2	Drug-induced Nephrotoxicity:	0.121
Genotoxicity:	0.032	RPMI-8226 Immunitoxicity:	0.024
A549 Cytotoxicity:	0.038	Hek293 Cytotoxicity:	0.261
BCF:	1.103 ? 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:	4.187 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.589 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.062 ? 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
NPO22879	Croton tonkinensis	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14510600]
NPO22879	Croton tonkinensis	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18161942]
NPO22879	Croton tonkinensis	Species	Euphorbiaceae	Eukaryota	n.a.	Vietnamese	n.a.	PMID[19899773]
NPO22879	Croton tonkinensis	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22085418]
NPO22879	Croton tonkinensis	Species	Euphorbiaceae	Eukaryota	n.a.	leaf	n.a.	PMID[22085418]
NPO22879	Croton tonkinensis	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22197145]
NPO22879	Croton tonkinensis	Species	Euphorbiaceae	Eukaryota	whole plants	Vietnam	2009-Aug	PMID[23347584]
NPO22879	Croton tonkinensis	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22879	Croton tonkinensis	Species	Euphorbiaceae	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

Activity Type	# Activity
IC50	2

Activity Type	# Activity
Non-molecular	2

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
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	5560.0	nM	PMID[23347584]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	3270.0	nM	PMID[23347584]

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 NPC471035 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	25151
0.1-0.2	22244
0.2-0.3	2180
0.3-0.4	153
0.4-0.5	92
0.5-0.6	23
0.6-0.7	5
0.7-0.8	0
0.8-0.85	0
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	NPC212661
0.6786	Remote Similarity	NPC211403
0.6167	Remote Similarity	NPC475118
0.6038	Remote Similarity	NPC330659
0.6038	Remote Similarity	NPC244708
0.6038	Remote Similarity	NPC161187
0.5818	Remote Similarity	NPC170985
0.5614	Remote Similarity	NPC600598
0.5556	Remote Similarity	NPC488959
0.5556	Remote Similarity	NPC106078
0.55	Remote Similarity	NPC472505
0.5345	Remote Similarity	NPC472309
0.5254	Remote Similarity	NPC215893
0.5185	Remote Similarity	NPC130459
0.5185	Remote Similarity	NPC474221
0.5185	Remote Similarity	NPC605656
0.5167	Remote Similarity	NPC472310
0.5167	Remote Similarity	NPC472311
0.5088	Remote Similarity	NPC99154
0.5088	Remote Similarity	NPC201027
0.5088	Remote Similarity	NPC268736
0.5088	Remote Similarity	NPC252032
0.5088	Remote Similarity	NPC319671
0.5088	Remote Similarity	NPC477931
0.5088	Remote Similarity	NPC476734
0.5085	Remote Similarity	NPC180199
0.5085	Remote Similarity	NPC471475
0.5085	Remote Similarity	NPC477919
0.5077	Remote Similarity	NPC257942

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC471035 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5922
0.1-0.2	3133
0.2-0.3	94
0.3-0.4	0
0.4-0.5	0
0.5-0.6	1
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
0.5263	Remote Similarity	NPD4224	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