NPASS Compound

Natural Product: NPC597000

Natural Product ID	NPC597000
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	6-Methylapigenin
IUPAC Name	5,7-dihydroxy-2-(4-hydroxyphenyl)-6-methyl-chromen-4-one
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 33 35 0 0 0 0 0 0 0 0999 V2000 5.2751 0.0862 0.2313 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8047 -0.0265 0.3500 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2124 -0.5614 1.4712 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0455 -0.9976 2.5001 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8409 -0.6572 1.5616 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0217 -0.2136 0.5177 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2819 -0.3049 0.6041 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0766 0.1099 -0.3745 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5286 -0.0134 -0.2309 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4371 0.3813 -1.1754 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8180 0.2385 -0.9827 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3105 -0.3113 0.1799 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6701 -0.4734 0.4166 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3999 -0.7111 1.1357 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0388 -0.5702 0.9454 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5289 0.6517 -1.5146 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8333 0.7713 -1.6580 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3917 1.2509 -2.6607 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6169 0.3217 -0.6041 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9957 0.4065 -0.6697 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5217 0.9611 -1.8397 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6153 -0.6923 -0.5080 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7282 -0.1960 1.1893 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6171 1.0763 -0.0621 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9705 -0.6439 3.4323 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3868 -1.0779 2.4443 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0951 0.8171 -2.1011 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5063 0.5620 -1.7520 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3715 -0.0038 -0.1428 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8072 -1.1488 2.0599 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3383 -0.8872 1.7015 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1395 1.0113 -2.3563 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4709 0.8450 -2.1374 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 3 5 1 0 5 6 2 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 12 14 1 0 14 15 2 0 8 16 2 0 16 17 1 0 17 18 2 0 17 19 1 0 19 20 2 0 20 21 1 0 20 2 1 0 19 6 1 0 15 9 1 0 1 22 1 0 1 23 1 0 1 24 1 0 4 25 1 0 5 26 1 0 10 27 1 0 11 28 1 0 13 29 1 0 14 30 1 0 15 31 1 0 16 32 1 0 21 33 1 0 M END

Standard InCHIKey	ZLGRXDWWYMFIGI-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C16H12O5/c1-8-11(18)6-14-15(16(8)20)12(19)7-13(21-14)9-2-4-10(17)5-3-9/h2-7,17-18,20H,1H3
SMILES	CC1=C(O)C=C2OC(C3=CC=C(O)C=C3)=CC(=O)C2=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	284.07	Volume:	282.482 ? Van der Waals volume.
Dense:	1.006	LogP:	2.979 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.444 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.118 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	18.0
TPSA:	90.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.639	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.376	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:	0.797	Fluc inhibitor:	0.986 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.982 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.74 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.574	Promiscuous compounds:	0.514

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.039	MDCK Permeability:	-4.759
Pgp-inhibitor:	0.024	Pgp-substrate:	0.075
PAMPA:	0.806 ? 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%):	0.506	30% Bioavailability (F30%):	0.554
50% Bioavailability (F50%):	0.954

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.008	MRP1:	0.793
Plasma Protein Binding (PPB):	96.861%	Volume Distribution (VD):	-0.407
Fu:	3.497% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.983
OATP1B3 inhibitor:	0.977	BCRP inhibitor:	0.528
BSEP inhibitor:	0.853

ADMET: Metabolism

CYP1A2-inhibitor:	0.21	CYP1A2-substrate:	0.232
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.005
CYP2C9-inhibitor:	0.669	CYP2C9-substrate:	0.028
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.102
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.539 ? 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):

7.489

Half-life (T1/2):

1.094

ADMET: Toxicity

hERG Blockers:	0.062	hERG Blockers (10um):	0.483
Human Hepatotoxicity (H-HT):	0.461	Drug-induced Liver Injury (DILI):	0.591
AMES Toxicity:	0.604	Rat Oral Acute Toxicity:	0.555
Maximum Recommended Daily Dose:	0.815	Skin Sensitization:	0.777
Carcinogencity:	0.691	Eye Corrosion:	0.308
Eye Irritation:	0.997	Respiratory Toxicity:	0.929
Drug-induced Neurotoxicity:	0.067	Ototoxicity:	0.105
Hematotoxicity:	0.085	Drug-induced Nephrotoxicity:	0.035
Genotoxicity:	0.986	RPMI-8226 Immunitoxicity:	0.07
A549 Cytotoxicity:	0.37	Hek293 Cytotoxicity:	0.826
BCF:	1.182 ? 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:	3.945 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.653 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.284 ? 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
NPO52841	Valeriana wallichii	Species	Caprifoliaceae	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

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 NPC597000 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	30396
0.1-0.2	16510
0.2-0.3	2179
0.3-0.4	548
0.4-0.5	168
0.5-0.6	37
0.6-0.7	10
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
0.8125	Intermediate Similarity	NPC201395
0.6964	Remote Similarity	NPC284220
0.6923	Remote Similarity	NPC473042
0.6724	Remote Similarity	NPC486096
0.661	Remote Similarity	NPC603717
0.6545	Remote Similarity	NPC78913
0.65	Remote Similarity	NPC189706
0.6471	Remote Similarity	NPC50898
0.6346	Remote Similarity	NPC130230
0.6182	Remote Similarity	NPC241498
0.6182	Remote Similarity	NPC482122
0.5909	Remote Similarity	NPC611357
0.5821	Remote Similarity	NPC328740
0.5821	Remote Similarity	NPC289774
0.5738	Remote Similarity	NPC3825
0.569	Remote Similarity	NPC159275
0.566	Remote Similarity	NPC172262
0.5574	Remote Similarity	NPC270883
0.5556	Remote Similarity	NPC476185
0.5556	Remote Similarity	NPC12367
0.5517	Remote Similarity	NPC198826
0.5517	Remote Similarity	NPC234133
0.5517	Remote Similarity	NPC120163
0.549	Remote Similarity	NPC108113
0.5469	Remote Similarity	NPC59210
0.5469	Remote Similarity	NPC265932
0.5455	Remote Similarity	NPC222713
0.537	Remote Similarity	NPC216318
0.5357	Remote Similarity	NPC279121
0.5345	Remote Similarity	NPC47815
0.5323	Remote Similarity	NPC67322
0.5312	Remote Similarity	NPC55018
0.5273	Remote Similarity	NPC22783
0.5273	Remote Similarity	NPC78540
0.5254	Remote Similarity	NPC18260
0.5231	Remote Similarity	NPC14871
0.52	Remote Similarity	NPC479643
0.5179	Remote Similarity	NPC275772
0.5179	Remote Similarity	NPC296197
0.5172	Remote Similarity	NPC607196
0.5161	Remote Similarity	NPC220062
0.5147	Remote Similarity	NPC602497
0.5085	Remote Similarity	NPC71334
0.5085	Remote Similarity	NPC301323
0.5085	Remote Similarity	NPC275836
0.5077	Remote Similarity	NPC138299
0.5077	Remote Similarity	NPC111112
0.507	Remote Similarity	NPC476280

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC597000 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5859
0.1-0.2	3197
0.2-0.3	85
0.3-0.4	7
0.4-0.5	1
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
0.5357	Remote Similarity	NPD1511	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