NPASS Compound

Natural Product: NPC477841

Natural Product ID	NPC477841
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2,3,2'',3''-Tetrahydroochnaflavone
IUPAC Name	2-[4-[5-(5,7-dihydroxy-4-oxo-2,3-dihydrochromen-2-yl)-2-hydroxyphenoxy]phenyl]-5,7-dihydroxy-2,3-dihydrochromen-4-one
Synonyms	2,3,2',3'-Tetrahydroochnaflavone
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	11478288
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001586] Biflavonoids and polyflavonoids

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 62 67 0 0 0 0 0 0 0 0999 V2000 -5.1046 -1.5940 -0.8696 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5382 -0.3538 -0.2270 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1855 -0.1113 1.0317 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5743 -0.0401 1.0186 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2956 0.6320 2.0006 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6730 0.7040 1.9898 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.3837 0.0940 0.9768 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.7018 -0.5813 -0.0138 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3239 -0.6353 0.0250 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5811 -1.3516 -1.0239 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2091 -1.7403 -2.0215 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.4419 -1.1853 -1.0202 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.3688 1.3771 2.9756 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0821 -0.4514 0.0167 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1575 0.1837 -0.7852 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7969 0.0708 -0.5277 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3143 -0.6726 0.5284 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2434 -1.3109 1.3349 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5695 -1.1853 1.0626 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0521 -0.7852 0.7830 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9237 -0.2410 -0.1408 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9767 -0.6974 -1.4513 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8405 -0.1615 -2.3724 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6866 0.8673 -1.9819 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6617 1.3432 -0.6944 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7717 0.7816 0.2296 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5461 2.4358 -0.2515 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6505 2.7168 -1.2163 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6138 1.5847 -1.2851 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2616 1.3749 -2.3088 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7835 0.7216 -0.1213 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6603 -0.3289 -0.1309 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7972 -1.1206 0.9766 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0480 -0.8566 2.1049 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1591 0.1907 2.1463 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0405 0.9784 1.0067 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1409 2.0595 1.0111 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1875 -1.6606 3.2288 O 0 0 0 0 0 0 0 0 0 0 0 0 8.4229 -0.6081 -1.2609 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0962 -1.7411 -1.7802 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9086 -2.4762 -0.2293 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6700 -1.7201 -1.8609 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7507 0.5243 -0.8754 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7251 1.1079 2.7924 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.4799 0.1398 0.9501 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4663 -0.7307 -1.9415 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2554 2.3730 3.0618 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5164 0.7706 -1.6179 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1033 0.6080 -1.1974 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8445 -1.8912 2.1614 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3002 -1.6869 1.6963 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8775 -0.5154 -3.3789 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3861 1.3194 -2.6730 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7653 1.1729 1.2512 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0019 3.3892 -0.0613 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2610 3.0387 -2.1884 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1943 3.6175 -0.8076 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4857 -1.9734 1.0181 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5529 0.4200 3.0313 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2439 -2.6631 3.2003 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3891 -0.9149 -1.2123 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0870 -2.6114 -1.2863 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 8 12 1 0 6 13 1 0 2 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 17 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 25 27 1 0 27 28 1 0 28 29 1 0 29 30 2 0 29 31 1 0 31 32 2 0 32 33 1 0 33 34 2 0 34 35 1 0 35 36 2 0 36 37 1 0 34 38 1 0 32 39 1 0 22 40 1 0 10 1 1 0 9 4 1 0 19 14 1 0 26 21 1 0 37 27 1 0 36 31 1 0 1 41 1 0 1 42 1 0 2 43 1 0 5 44 1 0 7 45 1 0 12 46 1 0 13 47 1 0 15 48 1 0 16 49 1 0 18 50 1 0 19 51 1 0 23 52 1 0 24 53 1 0 26 54 1 0 27 55 1 0 28 56 1 0 28 57 1 0 33 58 1 0 35 59 1 0 38 60 1 0 39 61 1 0 40 62 1 0 M END

Standard InCHIKey	XEODGBSMXJKQNI-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C30H22O10/c31-16-8-20(34)29-22(36)12-24(39-27(29)10-16)14-1-4-18(5-2-14)38-26-7-15(3-6-19(26)33)25-13-23(37)30-21(35)9-17(32)11-28(30)40-25/h1-11,24-25,31-35H,12-13H2
SMILES	C1C(OC2=CC(=CC(=C2C1=O)O)O)C3=CC=C(C=C3)OC4=C(C=CC(=C4)C5CC(=O)C6=C(C=C(C=C6O5)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	542.12	Volume:	527.089 ? Van der Waals volume.
Dense:	1.029	LogP:	3.928 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.009 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.615 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	36.0
TPSA:	162.98 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	5.0	Rings:	6.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.225	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.73	Fsp³:	0.133
MCE-18:	113.235 ? 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:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.992	Fluc inhibitor:	0.773 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.603 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.821 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.457	Promiscuous compounds:	0.006

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.31	MDCK Permeability:	-4.811
Pgp-inhibitor:	0.994	Pgp-substrate:	0.006
PAMPA:	0.105 ? 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):	0.001
20% Bioavailability (F20%):	0.003	30% Bioavailability (F30%):	0.987
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.925
Plasma Protein Binding (PPB):	96.234%	Volume Distribution (VD):	0.152
Fu:	4.185% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.992
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	1.0
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.991	CYP1A2-substrate:	0.999
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.978	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.598	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.007
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.997 ? 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):

3.748

Half-life (T1/2):

1.611

ADMET: Toxicity

hERG Blockers:	0.161	hERG Blockers (10um):	0.674
Human Hepatotoxicity (H-HT):	0.728	Drug-induced Liver Injury (DILI):	0.93
AMES Toxicity:	0.882	Rat Oral Acute Toxicity:	0.76
Maximum Recommended Daily Dose:	0.966	Skin Sensitization:	0.367
Carcinogencity:	0.783	Eye Corrosion:	0.0
Eye Irritation:	0.973	Respiratory Toxicity:	0.908
Drug-induced Neurotoxicity:	0.07	Ototoxicity:	0.425
Hematotoxicity:	0.079	Drug-induced Nephrotoxicity:	0.27
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.202
A549 Cytotoxicity:	0.931	Hek293 Cytotoxicity:	0.991
BCF:	1.647 ? 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:	4.559 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.53 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.927 ? 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
NPO21239	Quintinia acutifolia	Species	Paracryphiaceae	Eukaryota	Leaves	Charleston, New Zealand	1997-JAN	PMID[15104507]
NPO21239	Quintinia acutifolia	Species	Paracryphiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21239	Quintinia acutifolia	Species	Paracryphiaceae	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

Activity Type	# Activity
IC50	1

Activity Type	# Activity
Cell line	1

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
NPT168	Cell line	P388	Mus musculus	IC50	=	8.2	ug/ml	PMID[15104507]

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 NPC477841 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	27376
0.1-0.2	19121
0.2-0.3	2628
0.3-0.4	522
0.4-0.5	153
0.5-0.6	38
0.6-0.7	13
0.7-0.8	1
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
0.7458	Intermediate Similarity	NPC477840
0.7368	Intermediate Similarity	NPC236637
0.7358	Intermediate Similarity	NPC32441
0.7358	Intermediate Similarity	NPC79943
0.6786	Remote Similarity	NPC274784
0.6786	Remote Similarity	NPC20709
0.6727	Remote Similarity	NPC243083
0.6727	Remote Similarity	NPC13768
0.6727	Remote Similarity	NPC287246
0.6667	Remote Similarity	NPC321011
0.6667	Remote Similarity	NPC294852
0.6667	Remote Similarity	NPC188679
0.6441	Remote Similarity	NPC302950
0.625	Remote Similarity	NPC182421
0.6207	Remote Similarity	NPC338131
0.614	Remote Similarity	NPC295261
0.614	Remote Similarity	NPC296490
0.5932	Remote Similarity	NPC107586
0.5909	Remote Similarity	NPC108456
0.5862	Remote Similarity	NPC12296
0.5846	Remote Similarity	NPC109223
0.5846	Remote Similarity	NPC10937
0.5652	Remote Similarity	NPC611447
0.5542	Remote Similarity	NPC219927
0.5542	Remote Similarity	NPC611172
0.5507	Remote Similarity	NPC312973
0.5429	Remote Similarity	NPC69531
0.541	Remote Similarity	NPC329203
0.541	Remote Similarity	NPC324386
0.541	Remote Similarity	NPC222342
0.5395	Remote Similarity	NPC602605
0.5385	Remote Similarity	NPC258630
0.5323	Remote Similarity	NPC469764
0.5323	Remote Similarity	NPC606248
0.5312	Remote Similarity	NPC474836
0.5286	Remote Similarity	NPC475790
0.5256	Remote Similarity	NPC158188
0.5217	Remote Similarity	NPC174953
0.5161	Remote Similarity	NPC300668
0.5147	Remote Similarity	NPC17170
0.5143	Remote Similarity	NPC134783
0.5139	Remote Similarity	NPC118256
0.5135	Remote Similarity	NPC474038
0.5135	Remote Similarity	NPC26195
0.5085	Remote Similarity	NPC329225
0.5085	Remote Similarity	NPC147686
0.5082	Remote Similarity	NPC6407
0.5082	Remote Similarity	NPC545184
0.5082	Remote Similarity	NPC603284
0.5077	Remote Similarity	NPC171932
0.5072	Remote Similarity	NPC134171
0.5072	Remote Similarity	NPC106976
0.507	Remote Similarity	NPC200761
0.5068	Remote Similarity	NPC473272
0.5067	Remote Similarity	NPC475784

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC477841 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5036
0.1-0.2	4047
0.2-0.3	53
0.3-0.4	7
0.4-0.5	3
0.5-0.6	1
0.6-0.7	2
0.7-0.8	1
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
0.7358	Intermediate Similarity	NPD1552	Clinical (unspecified phase)
0.6727	Remote Similarity	NPD1550	Phase 2
0.6441	Remote Similarity	NPD1934	Phase 0
0.5085	Remote Similarity	NPD1549	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