NPASS Compound

Natural Product: NPC576402

Natural Product ID	NPC576402
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	7-O-methyl-8-chlorogenistein
IUPAC Name	8-chloro-5-hydroxy-3-(4-hydroxyphenyl)-7-methoxy-chromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002506] Isoflavonoids [CHEMONTID:0002586] O-methylated isoflavonoids [CHEMONTID:0002602] 7-O-methylated isoflavonoids [CHEMONTID:0002689] 7-O-methylisoflavones

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 33 35 0 0 0 0 0 0 0 0999 V2000 -6.2217 -0.0994 0.4911 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2086 0.7987 0.1574 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8576 0.4775 0.1545 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4425 -0.7924 0.4944 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0801 -1.1041 0.4879 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7221 -2.3846 0.8349 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1242 -0.1698 0.1479 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2252 -0.4689 0.1387 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5952 -1.6323 0.4508 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1086 0.5295 -0.2148 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5303 0.2695 -0.2406 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3061 0.6995 -1.2954 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6777 0.4624 -1.3453 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2803 -0.2209 -0.3132 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6566 -0.4509 -0.3775 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5151 -0.6535 0.7428 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1515 -0.4129 0.7834 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6405 1.7836 -0.5463 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6354 2.0045 -0.5196 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5368 1.1118 -0.1956 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8847 1.3868 -0.1794 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3810 3.0062 -0.6152 Cl 0 0 0 0 0 0 0 0 0 0 0 0 -5.8932 -0.6826 1.3925 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2808 -0.8676 -0.3316 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1797 0.3873 0.6709 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1596 -1.5537 0.7669 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3841 -2.9963 0.1148 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8981 1.2408 -2.1376 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2958 0.7962 -2.1698 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1221 -1.0795 0.2646 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0341 -1.1917 1.5402 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6223 -0.7874 1.6507 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3326 2.5941 -0.8315 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 5 7 2 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 14 16 1 0 16 17 2 0 10 18 2 0 18 19 1 0 19 20 1 0 20 21 2 0 21 22 1 0 21 3 1 0 20 7 1 0 17 11 1 0 1 23 1 0 1 24 1 0 1 25 1 0 4 26 1 0 6 27 1 0 12 28 1 0 13 29 1 0 15 30 1 0 16 31 1 0 17 32 1 0 18 33 1 0 M END

Standard InCHIKey	FLTULSFWLIRRSK-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C16H11ClO5/c1-21-12-6-11(19)13-15(20)10(7-22-16(13)14(12)17)8-2-4-9(18)5-3-8/h2-7,18-19H,1H3
SMILES	COC1=CC(O)=C2C(=O)C(C3=CC=C(O)C=C3)=COC2=C1Cl

Calculated Properties

Physi-Chem Properties

Molecular Weight:	318.03	Volume:	297.693 ? Van der Waals volume.
Dense:	1.068	LogP:	2.562 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.255 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.829 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	18.0
TPSA:	79.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.755	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.462	Fsp³:	0.062
MCE-18:	18.0 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.698	Fluc inhibitor:	0.849 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.922 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.653 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.629	Promiscuous compounds:	0.514

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.864	MDCK Permeability:	-4.722
Pgp-inhibitor:	0.056	Pgp-substrate:	0.051
PAMPA:	0.665 ? 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):	0.011
20% Bioavailability (F20%):	0.049	30% Bioavailability (F30%):	0.152
50% Bioavailability (F50%):	0.884

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.053	MRP1:	0.588
Plasma Protein Binding (PPB):	97.414%	Volume Distribution (VD):	-0.247
Fu:	1.922% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.954
OATP1B3 inhibitor:	0.971	BCRP inhibitor:	0.732
BSEP inhibitor:	0.876

ADMET: Metabolism

CYP1A2-inhibitor:	0.848	CYP1A2-substrate:	0.854
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.701
CYP2C9-inhibitor:	0.854	CYP2C9-substrate:	0.179
CYP2D6-inhibitor:	0.866	CYP2D6-substrate:	0.46
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.815
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.945
HLM stability:	0.047 ? 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):

8.129

Half-life (T1/2):

0.969

ADMET: Toxicity

hERG Blockers:	0.139	hERG Blockers (10um):	0.563
Human Hepatotoxicity (H-HT):	0.538	Drug-induced Liver Injury (DILI):	0.759
AMES Toxicity:	0.499	Rat Oral Acute Toxicity:	0.591
Maximum Recommended Daily Dose:	0.656	Skin Sensitization:	0.556
Carcinogencity:	0.654	Eye Corrosion:	0.076
Eye Irritation:	0.971	Respiratory Toxicity:	0.762
Drug-induced Neurotoxicity:	0.414	Ototoxicity:	0.272
Hematotoxicity:	0.197	Drug-induced Nephrotoxicity:	0.217
Genotoxicity:	0.81	RPMI-8226 Immunitoxicity:	0.071
A549 Cytotoxicity:	0.274	Hek293 Cytotoxicity:	0.527
BCF:	1.519 ? 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:	4.209 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.237 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.761 ? 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
NPO52160	Streptomyces sp. YIM GS3536	Genus	Streptomycetaceae	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 NPC576402 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	28535
0.1-0.2	17788
0.2-0.3	3022
0.3-0.4	385
0.4-0.5	110
0.5-0.6	17
0.6-0.7	2
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
0.6441	Remote Similarity	NPC303644
0.6	Remote Similarity	NPC131266
0.5932	Remote Similarity	NPC487222
0.5806	Remote Similarity	NPC483565
0.5738	Remote Similarity	NPC269451
0.5645	Remote Similarity	NPC216769
0.5484	Remote Similarity	NPC7013
0.5441	Remote Similarity	NPC24673
0.541	Remote Similarity	NPC487221
0.5323	Remote Similarity	NPC605229
0.5278	Remote Similarity	NPC605728
0.5238	Remote Similarity	NPC116632
0.5167	Remote Similarity	NPC39426
0.5156	Remote Similarity	NPC181124
0.5156	Remote Similarity	NPC162680
0.5156	Remote Similarity	NPC100971
0.5143	Remote Similarity	NPC219917
0.5079	Remote Similarity	NPC295384
0.5075	Remote Similarity	NPC114192

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC576402 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4498
0.1-0.2	4550
0.2-0.3	97
0.3-0.4	4
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
0.5167	Remote Similarity	NPD1510	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