NPASS Compound

Natural Product: NPC552600

Natural Product ID	NPC552600
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2s)-5,7,4'-trihydroxy-8-methoxyflavanone
IUPAC Name	(2~{S})-5,7-dihydroxy-2-(4-hydroxyphenyl)-8-methoxy-chroman-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 36 38 0 0 0 0 0 0 0 0999 V2000 -2.3797 -2.7773 0.5431 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3485 -1.9015 -0.5611 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5283 -0.5429 -0.4852 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7703 0.0400 -0.5909 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8861 -0.7661 -0.7809 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9736 1.4044 -0.5174 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8791 2.2275 -0.3287 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0055 3.6035 -0.2452 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6305 1.6420 -0.2224 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4313 0.2809 -0.2962 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1455 -0.2432 -0.1812 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9645 0.6128 -0.4662 C 0 0 2 0 0 0 0 0 0 0 0 0 2.2148 -0.1062 -0.1451 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2454 0.4772 0.5467 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4273 -0.1979 0.8518 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5584 -1.4945 0.4419 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7281 -2.1719 0.7404 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5490 -2.1240 -0.2567 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3899 -1.4305 -0.5446 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8046 1.8345 0.3812 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4717 2.5051 -0.0232 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5545 3.7540 -0.1870 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3023 -2.2595 1.5149 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5043 -3.4512 0.4728 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2746 -3.4087 0.5706 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4339 -1.1245 -0.0177 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9362 1.8687 -0.5983 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9130 3.9565 0.0643 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8898 0.8371 -1.5518 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1881 1.4928 0.8889 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2165 0.2997 1.4000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6210 -1.9186 0.3776 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6647 -3.1487 -0.5750 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5684 -1.8893 -1.0937 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7380 1.5319 1.4323 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6003 2.5878 0.2290 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 4 6 1 0 6 7 2 0 7 8 1 0 7 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 16 18 1 0 18 19 2 0 12 20 1 0 20 21 1 0 21 22 2 0 10 3 1 0 19 13 1 0 21 9 1 0 1 23 1 0 1 24 1 0 1 25 1 0 5 26 1 0 6 27 1 0 8 28 1 0 12 29 1 6 14 30 1 0 15 31 1 0 17 32 1 0 18 33 1 0 19 34 1 0 20 35 1 0 20 36 1 0 M END

Standard InCHIKey	OJCCBPWPNVUJFG-ZDUSSCGKSA-N
Standard InCHI	InChI=1S/C16H14O6/c1-21-15-12(20)6-10(18)14-11(19)7-13(22-16(14)15)8-2-4-9(17)5-3-8/h2-6,13,17-18,20H,7H2,1H3/t13-/m0/s1
SMILES	COC1=C(O)C=C(O)C2=C1O[C@H](C1=CC=C(O)C=C1)CC2=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	302.08	Volume:	293.909 ? Van der Waals volume.
Dense:	1.028	LogP:	2.619 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.745 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.102 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	18.0
TPSA:	96.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.789	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.0	Fsp³:	0.188
MCE-18:	57.789 ? 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:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.603	Fluc inhibitor:	0.74 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.318 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.296 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.349	Promiscuous compounds:	0.069

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.013	MDCK Permeability:	-4.789
Pgp-inhibitor:	0.503	Pgp-substrate:	0.166
PAMPA:	0.117 ? 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):	0.0
20% Bioavailability (F20%):	0.015	30% Bioavailability (F30%):	0.479
50% Bioavailability (F50%):	0.948

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.004	MRP1:	0.905
Plasma Protein Binding (PPB):	96.029%	Volume Distribution (VD):	-0.411
Fu:	4.777% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.735
OATP1B3 inhibitor:	0.993	BCRP inhibitor:	0.986
BSEP inhibitor:	0.846

ADMET: Metabolism

CYP1A2-inhibitor:	0.565	CYP1A2-substrate:	0.947
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.955
CYP2C9-inhibitor:	0.005	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.115	CYP2D6-substrate:	0.371
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.998
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.815
HLM stability:	0.961 ? 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):

4.417

Half-life (T1/2):

1.513

ADMET: Toxicity

hERG Blockers:	0.094	hERG Blockers (10um):	0.473
Human Hepatotoxicity (H-HT):	0.764	Drug-induced Liver Injury (DILI):	0.474
AMES Toxicity:	0.649	Rat Oral Acute Toxicity:	0.716
Maximum Recommended Daily Dose:	0.741	Skin Sensitization:	0.905
Carcinogencity:	0.352	Eye Corrosion:	0.065
Eye Irritation:	0.99	Respiratory Toxicity:	0.887
Drug-induced Neurotoxicity:	0.724	Ototoxicity:	0.356
Hematotoxicity:	0.16	Drug-induced Nephrotoxicity:	0.629
Genotoxicity:	0.962	RPMI-8226 Immunitoxicity:	0.141
A549 Cytotoxicity:	0.754	Hek293 Cytotoxicity:	0.666
BCF:	1.157 ? 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:	3.603 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.363 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.861 ? 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
NPO22168	Scutellaria rivularis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22168	Scutellaria rivularis	Species	Lamiaceae	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 NPC552600 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	25120
0.1-0.2	19721
0.2-0.3	4239
0.3-0.4	576
0.4-0.5	158
0.5-0.6	35
0.6-0.7	8
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
0.6346	Remote Similarity	NPC32441
0.6346	Remote Similarity	NPC79943
0.6346	Remote Similarity	NPC603284
0.6212	Remote Similarity	NPC181014
0.6111	Remote Similarity	NPC329203
0.6111	Remote Similarity	NPC222342
0.6	Remote Similarity	NPC475267
0.6	Remote Similarity	NPC606248
0.5714	Remote Similarity	NPC485881
0.5636	Remote Similarity	NPC37392
0.5593	Remote Similarity	NPC236637
0.5556	Remote Similarity	NPC225153
0.5556	Remote Similarity	NPC479876
0.5536	Remote Similarity	NPC274784
0.5536	Remote Similarity	NPC20709
0.5536	Remote Similarity	NPC324386
0.5536	Remote Similarity	NPC610021
0.55	Remote Similarity	NPC480991
0.5439	Remote Similarity	NPC469764
0.5439	Remote Similarity	NPC210084
0.541	Remote Similarity	NPC107572
0.541	Remote Similarity	NPC32739
0.5357	Remote Similarity	NPC20354
0.5357	Remote Similarity	NPC167624
0.5357	Remote Similarity	NPC166482
0.5357	Remote Similarity	NPC162869
0.5263	Remote Similarity	NPC300668
0.5254	Remote Similarity	NPC302950
0.5238	Remote Similarity	NPC470131
0.5238	Remote Similarity	NPC470133
0.5238	Remote Similarity	NPC220998
0.5238	Remote Similarity	NPC470132
0.5185	Remote Similarity	NPC329225
0.5185	Remote Similarity	NPC147686
0.5179	Remote Similarity	NPC243083
0.5179	Remote Similarity	NPC13768
0.5179	Remote Similarity	NPC287246
0.5172	Remote Similarity	NPC321011
0.5172	Remote Similarity	NPC294852
0.5172	Remote Similarity	NPC188679
0.5156	Remote Similarity	NPC134171
0.5079	Remote Similarity	NPC69674
0.5079	Remote Similarity	NPC477841

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC552600 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4366
0.1-0.2	4636
0.2-0.3	130
0.3-0.4	13
0.4-0.5	1
0.5-0.6	3
0.6-0.7	1
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
0.6346	Remote Similarity	NPD1552	Clinical (unspecified phase)
0.5254	Remote Similarity	NPD1934	Phase 0
0.5185	Remote Similarity	NPD1549	Phase 2
0.5179	Remote Similarity	NPD1550	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