NPASS Compound

Natural Product: NPC93552

Natural Product ID	NPC93552
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5,7,3',4'-Tetrahydroxy-2',5'-Di(3-Methylbut-2-Enyl)Isoflavone
IUPAC Name	3-[3,4-dihydroxy-2,5-bis(3-methylbut-2-enyl)phenyl]-5,7-dihydroxychromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2442950
PubChem CID	12096316
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002506] Isoflavonoids [CHEMONTID:0002901] Isoflav-2-enes [CHEMONTID:0000494] Isoflavones [CHEMONTID:0003580] 2'-prenylated isoflavones

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 57 59 0 0 0 0 0 0 0 0999 V2000 -6.2454 0.9775 0.5634 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4011 1.8003 -0.3268 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1236 2.0067 -0.0846 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3873 1.4421 1.0979 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2393 0.6700 0.5556 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9390 1.1886 0.6001 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1084 0.4523 0.0891 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0781 -0.7979 -0.4745 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0844 -1.5189 -0.9924 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8008 -2.7872 -1.6684 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2213 -3.9664 -1.3192 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8585 -5.1701 -2.0941 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0805 -4.1346 -0.1274 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3487 -1.3272 -0.5284 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3889 -0.5718 -0.0095 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6541 -1.1645 -0.0942 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5989 -2.5879 -1.0863 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4315 1.0683 0.1756 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8249 1.8558 -0.8856 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0046 2.4242 -0.8373 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8247 2.2770 0.1732 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0716 2.8887 0.2051 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9541 2.7513 1.2550 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5840 1.9685 2.3286 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3485 1.3435 2.3312 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4805 1.4986 1.2629 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2552 0.8772 1.2685 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8835 0.1592 2.2241 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9889 0.5675 3.4018 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2027 3.3822 1.2546 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0429 2.3992 -1.5234 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1086 -0.0979 0.4038 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3373 1.2029 0.4205 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0102 1.2801 1.6208 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5775 2.6395 -0.8124 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0680 0.7254 1.5867 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0265 2.2417 1.7724 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8049 2.1692 1.0439 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5780 -0.8354 -1.7445 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8432 -1.6052 -0.1776 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1670 -2.7052 -2.5692 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0414 -5.6222 -1.5812 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6785 -5.9017 -2.1961 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4663 -4.8868 -3.1151 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7375 -3.4528 0.6734 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9659 -5.1725 0.2983 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1671 -4.0349 -0.3551 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7362 -2.1109 0.2891 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1991 -2.7471 -1.8615 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1948 2.0209 -1.7557 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3233 3.4919 -0.6537 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2733 1.8576 3.1555 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3957 -0.3426 3.5686 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2923 4.2151 0.6765 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7288 3.2038 -1.1583 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3194 2.8472 -2.2243 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6861 1.6479 -2.0395 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 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 1 0 10 11 2 3 11 12 1 0 11 13 1 0 8 14 1 0 14 15 2 0 15 16 1 0 14 17 1 0 7 18 1 0 18 19 2 0 19 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 26 27 1 0 27 28 2 0 25 29 1 0 23 30 1 0 2 31 1 0 15 5 1 0 27 18 1 0 26 21 1 0 1 32 1 0 1 33 1 0 1 34 1 0 3 35 1 0 4 36 1 0 4 37 1 0 6 38 1 0 9 39 1 0 9 40 1 0 10 41 1 0 12 42 1 0 12 43 1 0 12 44 1 0 13 45 1 0 13 46 1 0 13 47 1 0 16 48 1 0 17 49 1 0 19 50 1 0 22 51 1 0 24 52 1 0 29 53 1 0 30 54 1 0 31 55 1 0 31 56 1 0 31 57 1 0 M END

Standard InCHIKey	RWGZXUWGOARVDQ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C25H26O6/c1-13(2)5-7-15-9-18(17(8-6-14(3)4)25(30)23(15)28)19-12-31-21-11-16(26)10-20(27)22(21)24(19)29/h5-6,9-12,26-28,30H,7-8H2,1-4H3
SMILES	CC(=CCc1cc(c(CC=C(C)C)c(c1O)O)c1coc2cc(cc(c2c1=O)O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	422.17	Volume:	441.663 ? Van der Waals volume.
Dense:	0.956	LogP:	4.215 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.392 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.616 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	20.0
TPSA:	111.13 ? 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:	0.328	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.223	Fsp³:	0.24
MCE-18:	22.0 ? 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:	1
Colloidal aggregators:	0.983	Fluc inhibitor:	0.571 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.87 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.353 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.52	Promiscuous compounds:	0.095

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.182	MDCK Permeability:	-4.805
Pgp-inhibitor:	0.047	Pgp-substrate:	0.03
PAMPA:	0.74 ? 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):	0.18
20% Bioavailability (F20%):	0.999	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.912
Plasma Protein Binding (PPB):	94.326%	Volume Distribution (VD):	0.145
Fu:	5.923% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.911
OATP1B3 inhibitor:	0.917	BCRP inhibitor:	1.0
BSEP inhibitor:	0.082

ADMET: Metabolism

CYP1A2-inhibitor:	0.017	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.998	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.084	CYP2C9-substrate:	0.632
CYP2D6-inhibitor:	0.97	CYP2D6-substrate:	0.161
CYP3A4-inhibitor:	0.002	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):

6.877

Half-life (T1/2):

1.237

ADMET: Toxicity

hERG Blockers:	0.044	hERG Blockers (10um):	0.538
Human Hepatotoxicity (H-HT):	0.615	Drug-induced Liver Injury (DILI):	0.86
AMES Toxicity:	0.742	Rat Oral Acute Toxicity:	0.923
Maximum Recommended Daily Dose:	0.908	Skin Sensitization:	0.875
Carcinogencity:	0.574	Eye Corrosion:	0.0
Eye Irritation:	0.547	Respiratory Toxicity:	0.972
Drug-induced Neurotoxicity:	0.255	Ototoxicity:	0.499
Hematotoxicity:	0.116	Drug-induced Nephrotoxicity:	0.599
Genotoxicity:	0.998	RPMI-8226 Immunitoxicity:	0.076
A549 Cytotoxicity:	0.667	Hek293 Cytotoxicity:	0.794
BCF:	2.046 ? 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:	5.151 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.804 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.296 ? 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
NPO4010	Flemingia philippinensis	Species	Fabaceae	Eukaryota	Roots	n.a.	n.a.	PMID[24054487]
NPO4010	Flemingia philippinensis	Species	Fabaceae	Eukaryota	roots	n.a.	n.a.	PMID[24412339]
NPO4010	Flemingia philippinensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4010	Flemingia philippinensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4010	Flemingia philippinensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4010	Flemingia philippinensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4010	Flemingia philippinensis	Species	Fabaceae	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
Ki	1
IC50	1

Activity Type	# Activity
Individual protein	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT344	Individual protein	Sialidase	Clostridium perfringens	Ki	=	7860.0	nM	DrugMatrix in vitro pharmacology data
NPT344	Individual protein	Sialidase	Clostridium perfringens	IC50	=	7850.0	nM	PMID[23398362]

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 NPC93552 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	26176
0.1-0.2	21243
0.2-0.3	1958
0.3-0.4	375
0.4-0.5	68
0.5-0.6	20
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
0.7705	Intermediate Similarity	NPC85131
0.7258	Intermediate Similarity	NPC238279
0.6875	Remote Similarity	NPC213659
0.6875	Remote Similarity	NPC326109
0.6364	Remote Similarity	NPC232947
0.6301	Remote Similarity	NPC303174
0.6176	Remote Similarity	NPC233918
0.6176	Remote Similarity	NPC268059
0.6087	Remote Similarity	NPC128774
0.6087	Remote Similarity	NPC485109
0.55	Remote Similarity	NPC193792
0.5493	Remote Similarity	NPC475705
0.5479	Remote Similarity	NPC488567
0.5432	Remote Similarity	NPC324447
0.5429	Remote Similarity	NPC203077
0.541	Remote Similarity	NPC39426
0.541	Remote Similarity	NPC608554
0.5333	Remote Similarity	NPC474960
0.5294	Remote Similarity	NPC476055
0.5238	Remote Similarity	NPC87545
0.5238	Remote Similarity	NPC38065
0.5231	Remote Similarity	NPC78341
0.5224	Remote Similarity	NPC309154
0.5152	Remote Similarity	NPC294409
0.5152	Remote Similarity	NPC490701
0.5139	Remote Similarity	NPC48624
0.5139	Remote Similarity	NPC169162
0.5075	Remote Similarity	NPC19980
0.5075	Remote Similarity	NPC239363
0.507	Remote Similarity	NPC205046

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC93552 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	4235
0.2-0.3	25
0.3-0.4	3
0.4-0.5	0
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
0.541	Remote Similarity	NPD1510	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