NPASS Compound

Natural Product: NPC12296

Natural Product ID	NPC12296
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2S)-2',5,6',7-Tetrahydroxyflavanone
IUPAC Name	(2S)-2-(2,6-dihydroxyphenyl)-5,7-dihydroxy-2,3-dihydrochromen-4-one
Synonyms	(2S)-2',5,6',7-Tetrahydroxyflavanone
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL465691
PubChem CID	157671
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0000337] Flavans [CHEMONTID:0001632] Flavanones

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 -4.1710 2.0547 1.9628 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4613 1.1382 1.1734 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1911 0.7936 1.5710 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4570 -0.1038 0.8251 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1902 -0.5024 1.1459 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7528 -1.1273 0.3076 C 0 0 1 0 0 0 0 0 0 0 0 0 0.2157 -1.5642 -1.0219 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2614 -1.5687 -1.0891 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8325 -2.3991 -1.8276 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0512 -0.6198 -0.3073 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3385 -0.2614 -0.6974 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0694 0.6370 0.0521 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8380 -0.8344 -1.8437 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9392 -0.2445 0.1269 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1814 -0.8322 0.0613 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2795 -2.2128 0.1657 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3019 -0.0445 -0.1061 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1822 1.3369 -0.2086 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9521 1.9381 -0.1453 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8274 1.1250 0.0246 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5607 1.6785 0.0951 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1467 1.9124 2.9646 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7127 1.1909 2.4574 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1255 -2.0348 0.8713 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5670 -0.8192 -1.7945 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6085 -2.5398 -1.3658 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0627 0.8921 -0.2789 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3610 -0.8042 -2.7414 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2083 -2.8459 -0.6006 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2584 -0.5025 -0.1562 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0695 1.9670 -0.3417 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7920 3.0064 -0.2184 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3225 2.1907 0.9399 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 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 1 0 11 12 2 0 11 13 1 0 6 14 1 0 14 15 2 0 15 16 1 0 15 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 12 2 1 0 20 14 1 0 10 4 2 0 1 22 1 0 3 23 1 0 6 24 1 1 7 25 1 0 7 26 1 0 12 27 1 0 13 28 1 0 16 29 1 0 17 30 1 0 18 31 1 0 19 32 1 0 21 33 1 0 M END

Standard InCHIKey	TWELZOKMSAJRKP-ZDUSSCGKSA-N
Standard InCHI	InChI=1S/C15H12O6/c16-7-4-10(19)15-11(20)6-13(21-12(15)5-7)14-8(17)2-1-3-9(14)18/h1-5,13,16-19H,6H2/t13-/m0/s1
SMILES	Oc1cc2O[C@@H](CC(=O)c2c(c1)O)c1c(O)cccc1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	288.06	Volume:	276.613 ? Van der Waals volume.
Dense:	1.041	LogP:	2.238 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.416 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.665 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	18.0
TPSA:	107.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.641	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.116	Fsp³:	0.133
MCE-18:	58.235 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.642	Fluc inhibitor:	0.756 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.369 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.178 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.472	Promiscuous compounds:	0.094

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.213	MDCK Permeability:	-4.803
Pgp-inhibitor:	0.095	Pgp-substrate:	0.21
PAMPA:	0.566 ? 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):	0.026
20% Bioavailability (F20%):	0.38	30% Bioavailability (F30%):	0.957
50% Bioavailability (F50%):	0.99

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.029	MRP1:	0.82
Plasma Protein Binding (PPB):	92.218%	Volume Distribution (VD):	0.118
Fu:	9.003% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.908
OATP1B3 inhibitor:	0.983	BCRP inhibitor:	0.869
BSEP inhibitor:	0.316

ADMET: Metabolism

CYP1A2-inhibitor:	0.998	CYP1A2-substrate:	0.165
CYP2C19-inhibitor:	0.005	CYP2C19-substrate:	0.986
CYP2C9-inhibitor:	0.977	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.999	CYP2D6-substrate:	0.985
CYP3A4-inhibitor:	0.849	CYP3A4-substrate:	0.198
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.335
HLM stability:	0.922 ? 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):

3.331

Half-life (T1/2):

1.593

ADMET: Toxicity

hERG Blockers:	0.02	hERG Blockers (10um):	0.468
Human Hepatotoxicity (H-HT):	0.826	Drug-induced Liver Injury (DILI):	0.247
AMES Toxicity:	0.789	Rat Oral Acute Toxicity:	0.62
Maximum Recommended Daily Dose:	0.845	Skin Sensitization:	0.939
Carcinogencity:	0.457	Eye Corrosion:	0.002
Eye Irritation:	0.996	Respiratory Toxicity:	0.449
Drug-induced Neurotoxicity:	0.208	Ototoxicity:	0.23
Hematotoxicity:	0.05	Drug-induced Nephrotoxicity:	0.544
Genotoxicity:	0.996	RPMI-8226 Immunitoxicity:	0.184
A549 Cytotoxicity:	0.783	Hek293 Cytotoxicity:	0.878
BCF:	1.202 ? 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:	3.645 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.677 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.973 ? 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
NPO29667	Scutellariae radix	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[9214730]

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	1

Activity Type	# Activity
Protein family	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1644	Protein family	Trypsin	Homo sapiens	IC50	>	1000000.0	nM	PMID[12713403]

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 NPC12296 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	26669
0.1-0.2	20011
0.2-0.3	2535
0.3-0.4	467
0.4-0.5	131
0.5-0.6	21
0.6-0.7	9
0.7-0.8	2
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
0.75	Intermediate Similarity	NPC107586
0.7083	Intermediate Similarity	NPC295261
0.7083	Intermediate Similarity	NPC32441
0.7083	Intermediate Similarity	NPC243083
0.7083	Intermediate Similarity	NPC13768
0.7083	Intermediate Similarity	NPC296490
0.7083	Intermediate Similarity	NPC287246
0.7083	Intermediate Similarity	NPC79943
0.6875	Remote Similarity	NPC182421
0.6667	Remote Similarity	NPC321011
0.6667	Remote Similarity	NPC294852
0.6667	Remote Similarity	NPC188679
0.6471	Remote Similarity	NPC274784
0.6471	Remote Similarity	NPC338131
0.6471	Remote Similarity	NPC20709
0.6182	Remote Similarity	NPC236637
0.6111	Remote Similarity	NPC302950
0.5962	Remote Similarity	NPC208176
0.5862	Remote Similarity	NPC477841
0.5789	Remote Similarity	NPC258630
0.5763	Remote Similarity	NPC109223
0.5763	Remote Similarity	NPC10937
0.55	Remote Similarity	NPC17170
0.541	Remote Similarity	NPC106976
0.5357	Remote Similarity	NPC310135
0.5323	Remote Similarity	NPC108456
0.5323	Remote Similarity	NPC174953
0.5323	Remote Similarity	NPC85121
0.5312	Remote Similarity	NPC88964
0.5312	Remote Similarity	NPC611447
0.5306	Remote Similarity	NPC482958
0.5238	Remote Similarity	NPC134783
0.5185	Remote Similarity	NPC472460
0.5156	Remote Similarity	NPC470890
0.5156	Remote Similarity	NPC312973
0.5156	Remote Similarity	NPC200761
0.5156	Remote Similarity	NPC475790
0.5077	Remote Similarity	NPC473990

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC12296 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4886
0.1-0.2	4179
0.2-0.3	72
0.3-0.4	9
0.4-0.5	1
0.5-0.6	0
0.6-0.7	1
0.7-0.8	2
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	NPD1550	Phase 2
0.7083	Intermediate Similarity	NPD1552	Clinical (unspecified phase)
0.6111	Remote Similarity	NPD1934	Phase 0

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