NPASS Compound

Natural Product: NPC249285

Natural Product ID	NPC249285
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	AFZMICRBFKZNIH-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	138052
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000472] Hydroxy acids and derivatives [CHEMONTID:0000299] Medium-chain hydroxy acids and derivatives

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 30 29 0 0 0 0 0 0 0 0999 V2000 0.4602 -0.9977 0.2823 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7466 -0.6257 1.0998 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9088 -0.2017 0.2623 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0925 0.1409 1.1754 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2270 0.5596 0.2641 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8122 1.6786 -0.4812 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9054 0.1719 -0.5315 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1263 -0.1318 -1.3659 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3177 -0.5415 -0.5548 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7889 0.4773 0.4029 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2692 1.6096 0.5256 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8775 0.2332 1.2580 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2809 -1.3752 0.9512 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1865 -1.8412 -0.4063 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5258 0.2407 1.7869 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0364 -1.4552 1.8040 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6982 0.7653 -0.2710 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2521 -0.9992 -0.4228 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8474 0.9694 1.8595 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4285 -0.7683 1.7413 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1088 0.7913 0.8877 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4122 -0.3021 -0.4354 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3876 1.4320 -1.3276 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0818 1.0330 0.1329 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0388 0.4550 -1.1907 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9391 -0.8609 -2.1560 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4059 0.8300 -1.8851 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0908 -1.5119 -0.0253 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1970 -0.7762 -1.2109 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5181 1.0007 1.5086 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 1 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 10 12 1 0 1 13 1 0 1 14 1 0 2 15 1 0 2 16 1 0 3 17 1 0 3 18 1 0 4 19 1 0 4 20 1 0 5 21 1 0 5 22 1 0 6 23 1 0 7 24 1 0 7 25 1 0 8 26 1 0 8 27 1 0 9 28 1 0 9 29 1 0 12 30 1 0 M END

Standard InCHIKey	AFZMICRBFKZNIH-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C9H18O3/c10-8-6-4-2-1-3-5-7-9(11)12/h10H,1-8H2,(H,11,12)
SMILES	C(CCCCO)CCCC(=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	174.13	Volume:	187.955 ? Van der Waals volume.
Dense:	0.926	LogP:	1.875 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.52 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.646 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	1.0
TPSA:	57.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	0.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.551	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	1.706	Fsp³:	0.889
MCE-18:	0.0 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.004	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.004 ? 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:	0.994	Promiscuous compounds:	0.844

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.111	MDCK Permeability:	-4.768
Pgp-inhibitor:	0.0	Pgp-substrate:	0.078
PAMPA:	0.974 ? 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):	0.716
20% Bioavailability (F20%):	0.158	30% Bioavailability (F30%):	0.438
50% Bioavailability (F50%):	0.14

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.182	MRP1:	0.944
Plasma Protein Binding (PPB):	83.427%	Volume Distribution (VD):	-0.087
Fu:	14.292% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.028
OATP1B3 inhibitor:	0.51	BCRP inhibitor:	0.027
BSEP inhibitor:	0.079

ADMET: Metabolism

CYP1A2-inhibitor:	0.041	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.127	CYP2C19-substrate:	0.194
CYP2C9-inhibitor:	0.999	CYP2C9-substrate:	0.009
CYP2D6-inhibitor:	0.013	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.099
CYP2B6-substrate:	0.899	CYP2C8-inhibitor:	0.655
HLM stability:	0.053 ? 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):

4.395

Half-life (T1/2):

1.15

ADMET: Toxicity

hERG Blockers:	0.03	hERG Blockers (10um):	0.106
Human Hepatotoxicity (H-HT):	0.459	Drug-induced Liver Injury (DILI):	0.195
AMES Toxicity:	0.136	Rat Oral Acute Toxicity:	0.081
Maximum Recommended Daily Dose:	0.084	Skin Sensitization:	0.651
Carcinogencity:	0.433	Eye Corrosion:	0.937
Eye Irritation:	0.997	Respiratory Toxicity:	0.642
Drug-induced Neurotoxicity:	0.068	Ototoxicity:	0.454
Hematotoxicity:	0.333	Drug-induced Nephrotoxicity:	0.398
Genotoxicity:	0.002	RPMI-8226 Immunitoxicity:	0.025
A549 Cytotoxicity:	0.004	Hek293 Cytotoxicity:	0.016
BCF:	0.177 ? 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:	2.743 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.992 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.312 ? 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
NPO26327	Chaenomeles sinensis	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14600382]
NPO26327	Chaenomeles sinensis	Species	Rosaceae	Eukaryota	Twigs	n.a.	n.a.	PMID[25894905]
NPO26327	Chaenomeles sinensis	Species	Rosaceae	Eukaryota	Twigs	n.a.	n.a.	PMID[28358502]
NPO26327	Chaenomeles sinensis	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3813	Chaenomeles speciosa	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26327	Chaenomeles sinensis	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO26327	Chaenomeles sinensis	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3813	Chaenomeles speciosa	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3813	Chaenomeles speciosa	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO3813	Chaenomeles speciosa	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO26327	Chaenomeles sinensis	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO26327	Chaenomeles sinensis	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3813	Chaenomeles speciosa	Species	Rosaceae	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

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 NPC249285 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	37895
0.1-0.2	10808
0.2-0.3	854
0.3-0.4	161
0.4-0.5	84
0.5-0.6	24
0.6-0.7	18
0.7-0.8	1
0.8-0.85	1
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	NPC604910
0.84	Intermediate Similarity	NPC317203
0.7083	Intermediate Similarity	NPC214610
0.7083	Intermediate Similarity	NPC118968
0.7083	Intermediate Similarity	NPC183424
0.7083	Intermediate Similarity	NPC294085
0.6667	Remote Similarity	NPC268826
0.6296	Remote Similarity	NPC171736
0.6296	Remote Similarity	NPC301585
0.6296	Remote Similarity	NPC261080
0.6296	Remote Similarity	NPC132565
0.6296	Remote Similarity	NPC209970
0.6296	Remote Similarity	NPC216630
0.6296	Remote Similarity	NPC201844
0.6296	Remote Similarity	NPC301696
0.6296	Remote Similarity	NPC196924
0.6296	Remote Similarity	NPC307783
0.6296	Remote Similarity	NPC154186
0.6296	Remote Similarity	NPC149184
0.6296	Remote Similarity	NPC279026
0.6296	Remote Similarity	NPC113928
0.6296	Remote Similarity	NPC14227
0.6071	Remote Similarity	NPC604140
0.6	Remote Similarity	NPC134782
0.5926	Remote Similarity	NPC155263
0.5769	Remote Similarity	NPC198126
0.5758	Remote Similarity	NPC324004
0.5758	Remote Similarity	NPC328497
0.5667	Remote Similarity	NPC180534
0.5667	Remote Similarity	NPC55023
0.5667	Remote Similarity	NPC21844
0.5667	Remote Similarity	NPC611531
0.5556	Remote Similarity	NPC175342
0.5484	Remote Similarity	NPC50457
0.5312	Remote Similarity	NPC34416
0.5312	Remote Similarity	NPC314679
0.5312	Remote Similarity	NPC281245
0.52	Remote Similarity	NPC18224
0.5152	Remote Similarity	NPC424
0.5152	Remote Similarity	NPC36061
0.5152	Remote Similarity	NPC69510
0.5152	Remote Similarity	NPC77272
0.5152	Remote Similarity	NPC8219
0.5152	Remote Similarity	NPC290563
0.5152	Remote Similarity	NPC139029
0.5152	Remote Similarity	NPC281972
0.5152	Remote Similarity	NPC261831
0.5152	Remote Similarity	NPC87564

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC249285 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6636
0.1-0.2	2196
0.2-0.3	241
0.3-0.4	58
0.4-0.5	10
0.5-0.6	5
0.6-0.7	3
0.7-0.8	1
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
0.7083	Intermediate Similarity	NPD9655	Phase 4
0.6296	Remote Similarity	NPD2270	Pre-clinical
0.6296	Remote Similarity	NPD633	Phase 3
0.6296	Remote Similarity	NPD9448	Phase 2
0.5769	Remote Similarity	NPD8618	Phase 4
0.5667	Remote Similarity	NPD622	Pre-clinical
0.5405	Remote Similarity	NPD3194	Phase 4
0.5152	Remote Similarity	NPD3195	Phase 2
0.5152	Remote Similarity	NPD3196	Approved

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