NPASS Compound

Natural Product: NPC471034

Natural Product ID	NPC471034
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	PHXVQRJHPRPGAN-XVLAHQNTSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2337571
PubChem CID	71720768
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 2D 53 56 0 0 0 0 0 0 0 0999 V2000 -0.7288 -6.0405 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7298 -5.6905 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1883 -5.3404 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2798 -6.8376 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6787 -5.5104 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5710 -4.3047 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9730 -2.9290 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4827 -2.7591 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5903 -3.9648 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1000 -3.7949 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4980 -2.4192 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5305 -1.3311 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 -1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8943 -1.3846 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6443 -0.0855 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8943 1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2760 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2458 1.6317 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 -0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4812 -1.1381 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3750 -1.5534 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1550 -7.4787 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8994 -7.1809 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0372 -4.3600 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3712 -8.3349 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8049 -7.1109 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7770 -6.9294 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4310 -6.9898 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0210 -6.1798 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6035 -5.3928 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8219 -3.4768 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4634 -2.7594 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4243 -1.4985 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5577 -5.0528 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3586 -4.1449 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3513 -5.2254 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7489 -3.2470 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9355 -1.8563 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4809 0.0574 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7934 0.8787 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1116 -0.3972 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8158 2.7115 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3038 1.7266 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6805 2.6860 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6004 0.7041 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6764 -0.5374 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0890 3.1235 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6161 1.0216 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4076 -0.4654 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8204 -1.9542 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8993 -0.1308 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 3 2 1 6 3 4 1 0 3 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 11 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 17 19 1 0 19 20 2 0 19 21 1 0 21 22 2 0 8 23 1 1 9 3 1 0 18 13 1 0 14 8 1 0 13 21 1 6 1 24 1 0 2 25 1 0 2 26 1 0 4 27 1 0 4 28 1 0 4 29 1 0 5 30 1 0 5 31 1 0 6 32 1 0 6 33 1 0 7 34 1 0 7 35 1 0 9 36 1 6 10 37 1 0 10 38 1 0 11 39 1 1 12 40 1 0 14 41 1 6 15 42 1 0 15 43 1 0 16 44 1 0 16 45 1 0 17 46 1 6 18 47 1 0 18 48 1 0 20 49 1 0 20 50 1 0 23 51 1 0 23 52 1 0 23 53 1 0 M END

Standard InCHIKey	PHXVQRJHPRPGAN-XVLAHQNTSA-N
Standard InCHI	InChI=1S/C20H30O3/c1-12-13-5-6-14-19(3)8-4-7-18(2,11-21)15(19)9-16(22)20(14,10-13)17(12)23/h13-16,21-22H,1,4-11H2,2-3H3/t13-,14-,15+,16-,18+,19-,20+/m0/s1
SMILES	OC[C@@]1(C)CCC[C@@]2([C@@H]1C[C@H](O)[C@]13[C@H]2CC[C@@H](C1)C(=C)C3=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	318.22	Volume:	341.348 ? Van der Waals volume.
Dense:	0.932	LogP:	2.637 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.918 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.695 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	21.0
TPSA:	57.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.731	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.832	Fsp³:	0.85
MCE-18:	101.432 ? 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:	0.295	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.013 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.426	Promiscuous compounds:	0.176

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.684	MDCK Permeability:	-4.659
Pgp-inhibitor:	0.027	Pgp-substrate:	0.143
PAMPA:	0.824 ? 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):	0.002
20% Bioavailability (F20%):	0.088	30% Bioavailability (F30%):	0.162
50% Bioavailability (F50%):	0.632

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.604	MRP1:	0.292
Plasma Protein Binding (PPB):	82.074%	Volume Distribution (VD):	0.165
Fu:	14.537% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.988
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.299
BSEP inhibitor:	0.705

ADMET: Metabolism

CYP1A2-inhibitor:	0.003	CYP1A2-substrate:	0.02
CYP2C19-inhibitor:	0.065	CYP2C19-substrate:	0.18
CYP2C9-inhibitor:	0.023	CYP2C9-substrate:	0.099
CYP2D6-inhibitor:	0.052	CYP2D6-substrate:	0.121
CYP3A4-inhibitor:	0.978	CYP3A4-substrate:	0.995
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.964
HLM stability:	0.382 ? 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):

9.586

Half-life (T1/2):

1.558

ADMET: Toxicity

hERG Blockers:	0.13	hERG Blockers (10um):	0.377
Human Hepatotoxicity (H-HT):	0.711	Drug-induced Liver Injury (DILI):	0.683
AMES Toxicity:	0.575	Rat Oral Acute Toxicity:	0.585
Maximum Recommended Daily Dose:	0.692	Skin Sensitization:	0.993
Carcinogencity:	0.875	Eye Corrosion:	0.007
Eye Irritation:	0.744	Respiratory Toxicity:	0.946
Drug-induced Neurotoxicity:	0.503	Ototoxicity:	0.5
Hematotoxicity:	0.754	Drug-induced Nephrotoxicity:	0.674
Genotoxicity:	0.669	RPMI-8226 Immunitoxicity:	0.12
A549 Cytotoxicity:	0.506	Hek293 Cytotoxicity:	0.745
BCF:	0.966 ? 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:	3.506 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.078 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.37 ? 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
Inhibition	1
IC50	1

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.	Inhibition	=	45.77	%	PMID[23347584]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	3950.0	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 NPC471034 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	19681
0.1-0.2	25951
0.2-0.3	3864
0.3-0.4	281
0.4-0.5	54
0.5-0.6	11
0.6-0.7	7
0.7-0.8	0
0.8-0.85	3
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	NPC190704
0.8085	Intermediate Similarity	NPC291320
0.8085	Intermediate Similarity	NPC259009
0.8085	Intermediate Similarity	NPC471036
0.717	Intermediate Similarity	NPC470386
0.7143	Intermediate Similarity	NPC80401
0.6909	Remote Similarity	NPC47853
0.6275	Remote Similarity	NPC488959
0.6275	Remote Similarity	NPC106078
0.6226	Remote Similarity	NPC483200
0.6111	Remote Similarity	NPC481535
0.6038	Remote Similarity	NPC149761
0.6034	Remote Similarity	NPC211403
0.5962	Remote Similarity	NPC308440
0.5769	Remote Similarity	NPC476316
0.5769	Remote Similarity	NPC600690
0.5593	Remote Similarity	NPC470387
0.5556	Remote Similarity	NPC91772
0.5556	Remote Similarity	NPC292374
0.5424	Remote Similarity	NPC470385
0.5263	Remote Similarity	NPC41070
0.5179	Remote Similarity	NPC231060
0.5082	Remote Similarity	NPC470388
0.5079	Remote Similarity	NPC329910

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC471034 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6617
0.1-0.2	2451
0.2-0.3	82
0.3-0.4	0
0.4-0.5	0
0.5-0.6	0
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
		NPD

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