NPASS Compound

Natural Product: NPC604340

Natural Product ID	NPC604340
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	OGURMTXRUQGVMS-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL40849
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 29 31 0 0 0 0 0 0 0 0999 V2000 4.4836 0.3784 -0.0286 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1317 -0.1667 -0.2349 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8786 -1.3906 -0.8333 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5927 -1.8660 -1.0080 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5101 -1.1197 -0.5831 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7446 0.1022 0.0151 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0412 0.5675 0.1843 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2759 1.8138 0.7947 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3788 0.9250 0.4802 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1101 2.0303 1.0186 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7549 0.4579 0.3139 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7900 1.2386 0.7537 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5737 2.4671 1.3561 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0830 0.8061 0.6007 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3269 -0.4311 -0.0047 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2582 -1.1912 -0.4358 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9613 -0.7784 -0.2928 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8609 -1.6111 -0.7617 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0566 -2.7278 -1.3093 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2051 -0.4748 0.1253 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8545 1.0011 -0.8482 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5600 0.9861 0.9058 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7377 -1.9505 -1.1543 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4012 -2.8123 -1.4708 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1064 1.9881 1.7635 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6162 3.2814 0.7448 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9299 1.3908 0.9335 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3558 -0.7831 -0.1303 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4671 -2.1311 -0.8946 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 6 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 12 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 7 2 1 0 17 11 1 0 18 5 1 0 1 20 1 0 1 21 1 0 1 22 1 0 3 23 1 0 4 24 1 0 8 25 1 0 13 26 1 0 14 27 1 0 15 28 1 0 16 29 1 0 M END

Standard InCHIKey	OGURMTXRUQGVMS-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C15H10O4/c1-7-5-6-9-12(13(7)17)15(19)11-8(14(9)18)3-2-4-10(11)16/h2-6,16-17H,1H3
SMILES	Cc1ccc2c(c1O)C(=O)c1c(O)cccc1C2=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	254.06	Volume:	256.396 ? Van der Waals volume.
Dense:	0.991	LogP:	3.823 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.192 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-6.416 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	18.0
TPSA:	74.6 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.644	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.169	Fsp³:	0.067
MCE-18:	36.0 ? 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:	1
Colloidal aggregators:	0.307	Fluc inhibitor:	0.81 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.302 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.432 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.802	Promiscuous compounds:	0.209

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.831	MDCK Permeability:	-4.779
Pgp-inhibitor:	0.893	Pgp-substrate:	0.097
PAMPA:	0.88 ? 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):	0.305
20% Bioavailability (F20%):	0.036	30% Bioavailability (F30%):	0.643
50% Bioavailability (F50%):	0.913

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.612
Plasma Protein Binding (PPB):	97.34%	Volume Distribution (VD):	0.345
Fu:	2.196% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.995
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.107
BSEP inhibitor:	0.756

ADMET: Metabolism

CYP1A2-inhibitor:	0.971	CYP1A2-substrate:	0.21
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.006
CYP2C9-inhibitor:	0.003	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.083
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.992
HLM stability:	0.722 ? 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):

3.509

Half-life (T1/2):

1.054

ADMET: Toxicity

hERG Blockers:	0.044	hERG Blockers (10um):	0.511
Human Hepatotoxicity (H-HT):	0.624	Drug-induced Liver Injury (DILI):	0.913
AMES Toxicity:	0.933	Rat Oral Acute Toxicity:	0.538
Maximum Recommended Daily Dose:	0.316	Skin Sensitization:	0.925
Carcinogencity:	0.823	Eye Corrosion:	0.003
Eye Irritation:	0.982	Respiratory Toxicity:	0.918
Drug-induced Neurotoxicity:	0.271	Ototoxicity:	0.386
Hematotoxicity:	0.749	Drug-induced Nephrotoxicity:	0.638
Genotoxicity:	0.845	RPMI-8226 Immunitoxicity:	0.284
A549 Cytotoxicity:	0.856	Hek293 Cytotoxicity:	0.438
BCF:	1.963 ? 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:	4.2 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.169 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.599 ? 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
NPO60995	Cassia alata	Species	Fabaceae	Eukaryota	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

Activity Type	# Activity
IC50	2

Activity Type	# Activity
Individual protein	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT278	Individual protein	Cathepsin G	Homo sapiens	IC50	=	55000.0	nM	PMID[1578486]
NPT279	Individual protein	Leukocyte elastase	Homo sapiens	IC50	=	9900.0	nM	PMID[1578486]

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 NPC604340 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	25978
0.1-0.2	20987
0.2-0.3	2535
0.3-0.4	254
0.4-0.5	72
0.5-0.6	20
0.6-0.7	5
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8	Intermediate Similarity	NPC103540
0.7576	Intermediate Similarity	NPC142956
0.7297	Intermediate Similarity	NPC205992
0.7097	Intermediate Similarity	NPC375356
0.697	Remote Similarity	NPC300274
0.697	Remote Similarity	NPC608834
0.6842	Remote Similarity	NPC416
0.6579	Remote Similarity	NPC282923
0.6316	Remote Similarity	NPC99731
0.5952	Remote Similarity	NPC257644
0.5854	Remote Similarity	NPC70622
0.5745	Remote Similarity	NPC115458
0.5556	Remote Similarity	NPC302783
0.5532	Remote Similarity	NPC272268
0.5455	Remote Similarity	NPC21599
0.5455	Remote Similarity	NPC288089
0.5455	Remote Similarity	NPC604901
0.5455	Remote Similarity	NPC608971
0.5417	Remote Similarity	NPC26924
0.5349	Remote Similarity	NPC487321
0.5333	Remote Similarity	NPC124365
0.5319	Remote Similarity	NPC242994
0.5238	Remote Similarity	NPC199253
0.5217	Remote Similarity	NPC1268
0.5208	Remote Similarity	NPC169452
0.5208	Remote Similarity	NPC193555
0.5143	Remote Similarity	NPC96915
0.5135	Remote Similarity	NPC602726
0.5106	Remote Similarity	NPC66593

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC604340 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4277
0.1-0.2	4642
0.2-0.3	223
0.3-0.4	6
0.4-0.5	0
0.5-0.6	1
0.6-0.7	0
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8	Intermediate Similarity	NPD1470	Phase 4
0.5135	Remote Similarity	NPD1201	Phase 4

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