NPASS Compound

Natural Product: NPC470462

Natural Product ID	NPC470462
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5,7,4'-Trihydroxy-3'-(4-Hydroxy-3-Methylbutyl)-5'-(3-Methyl-2-Buten-1-Yl)-3,6-Dimethyoxyflavone
IUPAC Name	5,7-dihydroxy-2-[4-hydroxy-3-(4-hydroxy-3-methylbutyl)-5-(3-methylbut-2-enyl)phenyl]-3,6-dimethoxychromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2037157
PubChem CID	46218174
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001615] Flavones [CHEMONTID:0003502] 3'-prenylated flavones

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 67 69 0 0 0 0 0 0 0 0999 V2000 -4.0896 4.1141 0.9153 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7721 2.6200 1.1312 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5029 2.5335 1.8737 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9280 1.1943 2.1650 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4687 0.3998 1.0148 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2522 -0.3603 0.2178 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7397 -1.0735 -0.8735 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3894 -0.9921 -1.1342 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4570 -0.2531 -0.3774 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1008 0.4442 0.7018 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9009 -0.1567 -0.5150 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6209 -1.0311 -1.2572 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0145 -0.9285 -1.3809 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6510 -1.7577 -2.0809 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6251 0.1055 -0.7084 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8531 0.9692 0.0360 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5540 0.8296 0.1173 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4985 2.0080 0.7095 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8641 2.1595 0.6296 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5995 1.2702 -0.1279 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9975 0.2390 -0.8024 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6817 -0.6787 -1.5729 O 0 0 0 0 0 0 0 0 0 0 0 0 7.9554 1.4261 -0.2021 O 0 0 0 0 0 0 0 0 0 0 0 0 8.5756 2.2175 -1.1838 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5174 3.1876 1.2941 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0444 -2.0855 -1.9364 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9831 -3.3153 -1.1810 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6212 -1.9132 -1.7173 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8895 -3.2017 -1.0639 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0635 -3.7103 -0.7571 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1480 -5.0597 -0.0809 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3163 -2.9895 -1.0744 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6190 -0.4971 0.4169 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9230 2.0364 1.9547 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0245 2.7217 3.1774 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5083 4.7369 1.6145 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1763 4.2712 0.9424 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7288 4.3544 -0.1034 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7407 2.1492 0.1596 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6768 3.0395 2.8835 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7325 3.2186 1.4074 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7271 0.6178 2.7320 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1047 1.2619 2.9472 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0414 -1.5241 -1.9862 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5255 1.0478 1.3343 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8975 2.6930 1.2975 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4686 -0.4417 -2.1480 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1682 3.2697 -1.1766 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6664 2.3484 -0.9183 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4335 1.7827 -2.1795 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0499 2.9816 2.1310 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9399 -3.6889 -1.1473 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3399 -3.1775 -0.1419 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6246 -4.0918 -1.6427 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0522 -2.1287 -2.6684 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5571 -1.3666 -1.9755 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0157 -3.8172 -0.8020 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5744 -5.0673 0.8610 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1949 -5.3436 0.0262 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6521 -5.7912 -0.7645 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1902 -3.6872 -1.1268 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5517 -2.2931 -0.2466 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2378 -2.4295 -2.0134 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2937 -0.1578 -0.2589 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6502 1.0086 2.2285 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8580 2.1173 1.3781 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3948 3.6348 3.0294 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 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 13 15 1 0 15 16 2 0 16 17 1 0 16 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 20 23 1 0 23 24 1 0 19 25 1 0 12 26 1 0 26 27 1 0 7 28 1 0 28 29 1 0 29 30 2 3 30 31 1 0 30 32 1 0 6 33 1 0 2 34 1 0 34 35 1 0 10 5 1 0 17 11 1 0 21 15 1 0 1 36 1 0 1 37 1 0 1 38 1 0 2 39 1 0 3 40 1 0 3 41 1 0 4 42 1 0 4 43 1 0 8 44 1 0 10 45 1 0 18 46 1 0 22 47 1 0 24 48 1 0 24 49 1 0 24 50 1 0 25 51 1 0 27 52 1 0 27 53 1 0 27 54 1 0 28 55 1 0 28 56 1 0 29 57 1 0 31 58 1 0 31 59 1 0 31 60 1 0 32 61 1 0 32 62 1 0 32 63 1 0 33 64 1 0 34 65 1 0 34 66 1 0 35 67 1 0 M END

Standard InCHIKey	HZKQZIBQTUUPIQ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C27H32O8/c1-14(2)6-8-16-10-18(11-17(22(16)30)9-7-15(3)13-28)25-27(34-5)24(32)21-20(35-25)12-19(29)26(33-4)23(21)31/h6,10-12,15,28-31H,7-9,13H2,1-5H3
SMILES	CC(CCC1=C(C(=CC(=C1)C2=C(C(=O)C3=C(O2)C=C(C(=C3O)OC)O)OC)CC=C(C)C)O)CO

Calculated Properties

Physi-Chem Properties

Molecular Weight:	484.21	Volume:	496.472 ? Van der Waals volume.
Dense:	0.975	LogP:	4.977 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.439 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.341 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	19.0
TPSA:	129.59 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.323	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.588	Fsp³:	0.37
MCE-18:	46.0 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.674	Fluc inhibitor:	0.326 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.897 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.896 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.044	Promiscuous compounds:	0.064

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.055	MDCK Permeability:	-4.75
Pgp-inhibitor:	0.935	Pgp-substrate:	0.032
PAMPA:	0.488 ? 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):	0.132
20% Bioavailability (F20%):	0.92	30% Bioavailability (F30%):	0.997
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.925
Plasma Protein Binding (PPB):	95.941%	Volume Distribution (VD):	-0.052
Fu:	3.683% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.07
OATP1B3 inhibitor:	0.839	BCRP inhibitor:	0.998
BSEP inhibitor:	0.976

ADMET: Metabolism

CYP1A2-inhibitor:	0.791	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.973	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.639	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.991
CYP3A4-inhibitor:	0.223	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

5.41

Half-life (T1/2):

1.009

ADMET: Toxicity

hERG Blockers:	0.056	hERG Blockers (10um):	0.549
Human Hepatotoxicity (H-HT):	0.655	Drug-induced Liver Injury (DILI):	0.234
AMES Toxicity:	0.289	Rat Oral Acute Toxicity:	0.314
Maximum Recommended Daily Dose:	0.47	Skin Sensitization:	0.963
Carcinogencity:	0.459	Eye Corrosion:	0.001
Eye Irritation:	0.675	Respiratory Toxicity:	0.623
Drug-induced Neurotoxicity:	0.068	Ototoxicity:	0.683
Hematotoxicity:	0.254	Drug-induced Nephrotoxicity:	0.325
Genotoxicity:	0.282	RPMI-8226 Immunitoxicity:	0.086
A549 Cytotoxicity:	0.45	Hek293 Cytotoxicity:	0.422
BCF:	1.689 ? 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:	4.378 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.856 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.283 ? 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
NPO12477	Dodonaea viscosa	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19719093]
NPO12477	Dodonaea viscosa	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22512738]
NPO12477	Dodonaea viscosa	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12477	Dodonaea viscosa	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12477	Dodonaea viscosa	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12477	Dodonaea viscosa	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12477	Dodonaea viscosa	Species	Sapindaceae	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
Activity	2

Activity Type	# Activity
Cell line	2

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
NPT520	Cell line	3T3-L1	Mus musculus	Activity	=	233.0	%	PMID[15568794]
NPT520	Cell line	3T3-L1	Mus musculus	Activity	=	289.8	%	PMID[15568794]

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 NPC470462 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	13697
0.1-0.2	31929
0.2-0.3	3710
0.3-0.4	476
0.4-0.5	27
0.5-0.6	9
0.6-0.7	3
0.7-0.8	0
0.8-0.85	3
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8194	Intermediate Similarity	NPC470456
0.8154	Intermediate Similarity	NPC246478
0.8056	Intermediate Similarity	NPC470460
0.7971	Intermediate Similarity	NPC470459
0.7746	Intermediate Similarity	NPC158761
0.7639	Intermediate Similarity	NPC470457
0.6389	Remote Similarity	NPC158874
0.6316	Remote Similarity	NPC470458
0.6125	Remote Similarity	NPC470461
0.5641	Remote Similarity	NPC97255
0.55	Remote Similarity	NPC269285
0.5493	Remote Similarity	NPC266960
0.5352	Remote Similarity	NPC472438
0.5278	Remote Similarity	NPC203891
0.527	Remote Similarity	NPC29841
0.5205	Remote Similarity	NPC163524
0.5135	Remote Similarity	NPC9609
0.5067	Remote Similarity	NPC115798

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC470462 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3015
0.1-0.2	6069
0.2-0.3	63
0.3-0.4	3
0.4-0.5	0
0.5-0.6	0
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
		NPD

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