NPASS Compound

Natural Product: NPC493850

Natural Product ID	NPC493850
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Labrenzide
IUPAC Name	4-[(1~{R},2~{S})-2-hexylcyclopropyl]butanoic acid
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 39 39 0 0 0 0 0 0 0 0999 V2000 -6.2005 0.3152 0.1087 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9428 0.1006 0.8962 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7964 -0.0071 -0.0880 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4663 -0.2308 0.6351 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4182 -0.3214 -0.4517 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0266 -0.5490 0.1457 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9294 -0.6261 -0.9974 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9369 0.6690 -1.8352 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1368 0.1741 -1.1484 C 0 0 1 0 0 0 0 0 0 0 0 0 2.7433 0.9632 -0.0303 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1565 0.1422 1.1471 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1900 -0.9074 0.8274 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4064 -0.2628 0.3076 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4642 0.1100 -0.9019 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5060 -0.0620 1.1593 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0738 -0.1197 -0.9076 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0438 -0.1744 0.6332 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3921 1.3885 0.0260 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7684 0.9838 1.5443 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0004 -0.8142 1.4963 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6836 0.9350 -0.6627 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9930 -0.8700 -0.7550 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2724 0.6279 1.3100 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5199 -1.1757 1.2194 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4525 0.6142 -1.0297 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6936 -1.1741 -1.1151 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1460 0.2856 0.8329 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0417 -1.4796 0.7485 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8342 -1.5777 -1.5868 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4677 1.5670 -1.4333 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8132 0.5078 -2.9340 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9177 -0.2513 -1.8451 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6579 1.5016 -0.3978 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0688 1.7673 0.3557 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3014 -0.3355 1.6652 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6274 0.8377 1.8829 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4333 -1.4153 1.7963 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8104 -1.7063 0.1589 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2382 0.5695 0.8500 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 2 0 13 15 1 0 9 7 1 0 1 16 1 0 1 17 1 0 1 18 1 0 2 19 1 0 2 20 1 0 3 21 1 0 3 22 1 0 4 23 1 0 4 24 1 0 5 25 1 0 5 26 1 0 6 27 1 0 6 28 1 0 7 29 1 6 8 30 1 0 8 31 1 0 9 32 1 6 10 33 1 0 10 34 1 0 11 35 1 0 11 36 1 0 12 37 1 0 12 38 1 0 15 39 1 0 M END

Standard InCHIKey	MQWFOICQHNOBOJ-NWDGAFQWSA-N
Standard InCHI	InChI=1S/C13H24O2/c1-2-3-4-5-7-11-10-12(11)8-6-9-13(14)15/h11-12H,2-10H2,1H3,(H,14,15)/t11-,12+/m0/s1
SMILES	CCCCCC[C@H]1C[C@H]1CCCC(=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	212.18	Volume:	239.792 ? Van der Waals volume.
Dense:	0.885	LogP:	4.421 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.188 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.688 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	4.0
TPSA:	37.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	1.0	Rings:	1.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.589	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.918	Fsp³:	0.923
MCE-18:	13.44 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.013	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.009 ? 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:	0.978	Promiscuous compounds:	0.59

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.057	MDCK Permeability:	-4.762
Pgp-inhibitor:	0.0	Pgp-substrate:	0.022
PAMPA:	0.508 ? 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):	0.183
20% Bioavailability (F20%):	0.124	30% Bioavailability (F30%):	0.711
50% Bioavailability (F50%):	0.294

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.046	MRP1:	0.915
Plasma Protein Binding (PPB):	95.707%	Volume Distribution (VD):	0.106
Fu:	4.637% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.683
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.032
BSEP inhibitor:	0.06

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.004
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.486
CYP2C9-inhibitor:	0.888	CYP2C9-substrate:	0.324
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.008	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.005	CYP2C8-inhibitor:	0.981
HLM stability:	0.0 ? 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):

3.029

Half-life (T1/2):

1.026

ADMET: Toxicity

hERG Blockers:	0.045	hERG Blockers (10um):	0.195
Human Hepatotoxicity (H-HT):	0.547	Drug-induced Liver Injury (DILI):	0.21
AMES Toxicity:	0.17	Rat Oral Acute Toxicity:	0.132
Maximum Recommended Daily Dose:	0.114	Skin Sensitization:	0.74
Carcinogencity:	0.406	Eye Corrosion:	0.954
Eye Irritation:	0.996	Respiratory Toxicity:	0.707
Drug-induced Neurotoxicity:	0.062	Ototoxicity:	0.5
Hematotoxicity:	0.388	Drug-induced Nephrotoxicity:	0.41
Genotoxicity:	0.001	RPMI-8226 Immunitoxicity:	0.031
A549 Cytotoxicity:	0.029	Hek293 Cytotoxicity:	0.033
BCF:	1.249 ? 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:	4.061 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.293 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.395 ? 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
NPO52027	Labrenzia sp.	Species	Stappiaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO53859	Labrenzia sp. 011	Species	Stappiaceae	Bacteria	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 NPC493850 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	34128
0.1-0.2	14026
0.2-0.3	1407
0.3-0.4	200
0.4-0.5	52
0.5-0.6	24
0.6-0.7	17
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
0.6207	Remote Similarity	NPC171736
0.6207	Remote Similarity	NPC301585
0.6207	Remote Similarity	NPC261080
0.6207	Remote Similarity	NPC132565
0.6207	Remote Similarity	NPC209970
0.6207	Remote Similarity	NPC216630
0.6207	Remote Similarity	NPC201844
0.6207	Remote Similarity	NPC301696
0.6207	Remote Similarity	NPC196924
0.6207	Remote Similarity	NPC307783
0.6207	Remote Similarity	NPC154186
0.6207	Remote Similarity	NPC149184
0.6207	Remote Similarity	NPC279026
0.6207	Remote Similarity	NPC113928
0.6207	Remote Similarity	NPC14227
0.6129	Remote Similarity	NPC55023
0.6129	Remote Similarity	NPC21844
0.5862	Remote Similarity	NPC155263
0.5758	Remote Similarity	NPC314679
0.5556	Remote Similarity	NPC174368
0.5517	Remote Similarity	NPC175342
0.5172	Remote Similarity	NPC214610
0.5172	Remote Similarity	NPC118968
0.5172	Remote Similarity	NPC183424
0.5172	Remote Similarity	NPC294085
0.5143	Remote Similarity	NPC129972
0.5143	Remote Similarity	NPC424
0.5143	Remote Similarity	NPC36061
0.5143	Remote Similarity	NPC69510
0.5143	Remote Similarity	NPC77272
0.5143	Remote Similarity	NPC8219
0.5143	Remote Similarity	NPC301528
0.5143	Remote Similarity	NPC290563
0.5143	Remote Similarity	NPC139029
0.5143	Remote Similarity	NPC281972
0.5143	Remote Similarity	NPC71317
0.5143	Remote Similarity	NPC92114
0.5143	Remote Similarity	NPC261831
0.5143	Remote Similarity	NPC87564
0.5143	Remote Similarity	NPC163746
0.5143	Remote Similarity	NPC103286

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC493850 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6143
0.1-0.2	2647
0.2-0.3	283
0.3-0.4	62
0.4-0.5	7
0.5-0.6	5
0.6-0.7	3
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
0.6207	Remote Similarity	NPD2270	Pre-clinical
0.6207	Remote Similarity	NPD633	Phase 3
0.6207	Remote Similarity	NPD9448	Phase 2
0.575	Remote Similarity	NPD3198	Phase 2
0.5172	Remote Similarity	NPD9655	Phase 4
0.5143	Remote Similarity	NPD3195	Phase 2
0.5143	Remote Similarity	NPD3196	Approved
0.5122	Remote Similarity	NPD3186	Phase 1

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