NPASS Compound

Natural Product: NPC472526

Natural Product ID	NPC472526
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	QOBIRJABWHKJBS-OACYRQNASA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	9824910
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002506] Isoflavonoids [CHEMONTID:0000507] Isoflavonoid O-glycosides

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 52 55 0 0 0 0 0 0 0 0999 V2000 4.2898 -0.7213 -1.8979 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5015 -1.2127 -2.3465 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5613 -1.3254 -1.4993 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4171 -0.9438 -0.1825 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1951 -0.4504 0.2614 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1020 -0.3236 -0.5712 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8433 0.1904 -0.0910 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6803 -0.4901 -0.4680 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5078 -0.1050 -0.0873 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2668 0.9437 0.6796 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4004 1.6483 1.0764 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6766 1.2841 0.7010 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7000 1.9203 1.0593 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2136 2.7489 1.8749 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0384 3.1609 2.2817 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1463 2.4239 1.8597 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9959 1.3194 1.0617 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0829 0.6131 0.6598 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8274 0.8383 -0.5149 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2530 1.1991 -0.2796 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2257 0.0929 -0.6270 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5867 -1.1868 -0.0689 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3508 -1.4013 -0.9145 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7351 -0.2536 -1.3269 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4261 -2.4255 -0.2916 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7658 -1.9896 0.8290 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3077 -0.9711 1.2588 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4293 0.3716 -0.0213 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6566 2.3244 -1.0027 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3939 2.8785 2.2964 O 0 0 0 0 0 0 0 0 0 0 0 0 7.5065 -1.0653 0.6660 O 0 0 0 0 0 0 0 0 0 0 0 0 7.7595 -1.8278 -2.0074 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4211 -0.6147 -2.5364 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5946 -1.5072 -3.3844 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0936 -0.1550 1.2927 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7701 -1.3736 -1.1037 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0896 3.3066 2.1908 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1829 4.0298 2.9119 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3244 1.6842 -1.0585 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4223 1.4356 0.7923 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3064 -0.0587 -1.7253 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3098 -1.9993 -0.1550 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7341 -1.9025 -1.8549 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7043 -2.7849 -1.0785 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0047 -3.3289 -0.0098 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8951 -2.4719 0.9009 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5793 -1.7564 1.7978 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1563 -0.2516 -0.2816 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2866 2.3572 -1.9047 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9927 2.3620 2.9071 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4466 -1.4931 1.5856 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0833 -2.7424 -1.6955 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 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 0 11 12 1 0 12 13 2 0 11 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 23 25 1 0 25 26 1 0 22 27 1 0 21 28 1 0 20 29 1 0 16 30 1 0 4 31 1 0 3 32 1 0 6 1 1 0 12 7 1 0 17 10 1 0 24 19 1 0 1 33 1 0 2 34 1 0 5 35 1 0 8 36 1 0 14 37 1 0 15 38 1 0 19 39 1 0 20 40 1 0 21 41 1 0 22 42 1 0 23 43 1 0 25 44 1 0 25 45 1 0 26 46 1 0 27 47 1 0 28 48 1 0 29 49 1 0 30 50 1 0 31 51 1 0 32 52 1 0 M END

Standard InCHIKey	QOBIRJABWHKJBS-OACYRQNASA-N
Standard InCHI	InChI=1S/C21H20O11/c22-6-14-16(27)17(28)18(29)21(31-14)32-20-12(24)4-2-9-15(26)10(7-30-19(9)20)8-1-3-11(23)13(25)5-8/h1-5,7,14,16-18,21-25,27-29H,6H2/t14-,16-,17+,18-,21+/m1/s1
SMILES	C1=CC(=C(C=C1C2=COC3=C(C2=O)C=CC(=C3OC4C(C(C(C(O4)CO)O)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	448.1	Volume:	413.147 ? Van der Waals volume.
Dense:	1.085	LogP:	-1.299 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.343 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.918 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	24.0
TPSA:	190.28 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	7.0	Rings:	4.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.261	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.964	Fsp³:	0.286
MCE-18:	87.63 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.423	Fluc inhibitor:	0.133 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.984 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.823 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.355	Promiscuous compounds:	0.671

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.365	MDCK Permeability:	-5.097
Pgp-inhibitor:	0.0	Pgp-substrate:	0.304
PAMPA:	0.999 ? 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):	0.957
20% Bioavailability (F20%):	0.996	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.004	MRP1:	0.725
Plasma Protein Binding (PPB):	76.862%	Volume Distribution (VD):	-0.171
Fu:	24.939% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.013
OATP1B3 inhibitor:	0.885	BCRP inhibitor:	0.501
BSEP inhibitor:	0.002

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.28	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.002	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.005
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.887
HLM stability:	0.005 ? 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):

5.255

Half-life (T1/2):

2.41

ADMET: Toxicity

hERG Blockers:	0.052	hERG Blockers (10um):	0.476
Human Hepatotoxicity (H-HT):	0.531	Drug-induced Liver Injury (DILI):	0.649
AMES Toxicity:	0.639	Rat Oral Acute Toxicity:	0.39
Maximum Recommended Daily Dose:	0.455	Skin Sensitization:	0.664
Carcinogencity:	0.254	Eye Corrosion:	0.0
Eye Irritation:	0.296	Respiratory Toxicity:	0.083
Drug-induced Neurotoxicity:	0.053	Ototoxicity:	0.964
Hematotoxicity:	0.052	Drug-induced Nephrotoxicity:	0.066
Genotoxicity:	0.745	RPMI-8226 Immunitoxicity:	0.042
A549 Cytotoxicity:	0.446	Hek293 Cytotoxicity:	0.435
BCF:	0.459 ? 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:	2.899 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.507 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.696 ? 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
NPO30303	Pueraria lobata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25679337]
NPO30303	Pueraria lobata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30303	Pueraria lobata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO30303	Pueraria lobata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]

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 NPC472526 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	20074
0.1-0.2	26034
0.2-0.3	2729
0.3-0.4	815
0.4-0.5	179
0.5-0.6	25
0.6-0.7	3
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
0.6375	Remote Similarity	NPC258035
0.6173	Remote Similarity	NPC161749
0.6071	Remote Similarity	NPC229729
0.5976	Remote Similarity	NPC105511
0.5976	Remote Similarity	NPC603782
0.5595	Remote Similarity	NPC282987
0.5595	Remote Similarity	NPC197896
0.5595	Remote Similarity	NPC313163
0.5542	Remote Similarity	NPC45165
0.5465	Remote Similarity	NPC100720
0.5465	Remote Similarity	NPC205076
0.5455	Remote Similarity	NPC307518
0.5455	Remote Similarity	NPC607201
0.5412	Remote Similarity	NPC156457
0.5393	Remote Similarity	NPC48773
0.5393	Remote Similarity	NPC479407
0.5357	Remote Similarity	NPC135345
0.5333	Remote Similarity	NPC264289
0.5301	Remote Similarity	NPC474434
0.5227	Remote Similarity	NPC224462
0.5185	Remote Similarity	NPC94777
0.5172	Remote Similarity	NPC73511
0.5169	Remote Similarity	NPC601607
0.5132	Remote Similarity	NPC473044
0.5116	Remote Similarity	NPC211014
0.5067	Remote Similarity	NPC69430
0.5057	Remote Similarity	NPC168822
0.5056	Remote Similarity	NPC481043

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC472526 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4931
0.1-0.2	4124
0.2-0.3	82
0.3-0.4	9
0.4-0.5	2
0.5-0.6	1
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
0.6173	Remote Similarity	NPD4381	Clinical (unspecified phase)
0.5357	Remote Similarity	NPD3818	Discontinued

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