NPASS Compound

Natural Product: NPC198030

Natural Product ID	NPC198030
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	MGJLSBDCWOSMHL-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	3733033
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 53 56 0 0 0 0 0 0 0 0999 V2000 9.7555 0.6163 0.8018 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1007 -0.2346 -0.0980 O 0 0 0 0 0 0 0 0 0 0 0 0 7.7007 -0.2575 -0.0704 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9742 0.5310 0.8133 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5985 0.4654 0.7936 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8846 -0.3471 -0.0622 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6443 -1.1216 -0.9319 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0218 -1.0895 -0.9486 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4333 -0.4185 -0.0852 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7358 -1.6048 -0.1450 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4117 -1.6317 -0.1643 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6800 -0.5438 -0.1284 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7067 -0.5928 -0.1496 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5213 0.5092 -0.1143 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8468 1.7402 -0.0530 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5087 1.8250 -0.0307 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2872 0.6890 -0.0680 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6844 0.7374 -0.0467 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2336 1.8590 0.0083 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8929 0.4828 -0.1343 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6559 -0.6513 -0.1925 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4267 -0.6300 -1.5021 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8902 -0.2954 -1.2227 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8896 0.8332 -0.1982 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3154 0.3044 1.0981 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4733 -0.1057 1.9833 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2122 -1.1190 1.3496 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5196 -0.8157 0.8933 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.2108 1.2369 -0.0550 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4175 0.2154 -2.3952 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3051 -1.8144 -2.2036 O 0 0 0 0 0 0 0 0 0 0 0 0 9.3509 1.6680 0.7357 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5928 0.2159 1.8305 H 0 0 0 0 0 0 0 0 0 0 0 0 10.8438 0.6543 0.6508 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5214 1.1735 1.4907 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0292 1.0761 1.4783 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1281 -1.7691 -1.6159 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6197 -1.6826 -1.6152 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3244 -2.5226 -0.1756 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1272 -1.5836 -0.1973 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4293 2.6543 -0.0224 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0610 2.7594 0.0164 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0461 -1.5653 -0.2222 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0633 0.1807 -2.1755 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4386 -1.1847 -0.8550 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2641 1.6335 -0.5905 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7768 1.1195 1.6335 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1111 -0.5449 2.9406 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1727 0.7482 2.1604 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1732 -0.9210 1.3313 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4705 1.9413 -0.6949 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2114 -0.4342 -3.1117 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5581 -2.3884 -1.8465 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 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 6 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 14 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 25 28 1 0 24 29 1 0 23 30 1 0 22 31 1 0 8 3 1 0 18 9 1 0 28 21 1 0 17 12 1 0 1 32 1 0 1 33 1 0 1 34 1 0 4 35 1 0 5 36 1 0 7 37 1 0 8 38 1 0 10 39 1 0 13 40 1 0 15 41 1 0 16 42 1 0 21 43 1 0 22 44 1 0 23 45 1 0 24 46 1 0 25 47 1 0 26 48 1 0 26 49 1 0 27 50 1 0 29 51 1 0 30 52 1 0 31 53 1 0 M END

Standard InCHIKey	MGJLSBDCWOSMHL-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C22H22O9/c1-28-12-4-2-11(3-5-12)15-10-29-16-8-13(6-7-14(16)18(15)24)30-22-21(27)20(26)19(25)17(9-23)31-22/h2-8,10,17,19-23,25-27H,9H2,1H3
SMILES	COc1ccc(cc1)c1coc2cc(ccc2c1=O)OC1C(C(C(C(CO)O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	430.13	Volume:	412.863 ? Van der Waals volume.
Dense:	1.042	LogP:	0.235 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.159 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.949 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	24.0
TPSA:	138.82 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	4.0	Rings:	4.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.459	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.588	Fsp³:	0.318
MCE-18:	80.276 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.222	Fluc inhibitor:	0.346 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.924 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.714 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.155	Promiscuous compounds:	0.159

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.125	MDCK Permeability:	-5.276
Pgp-inhibitor:	0.001	Pgp-substrate:	0.383
PAMPA:	0.991 ? 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):	0.996
20% Bioavailability (F20%):	0.696	30% Bioavailability (F30%):	0.978
50% Bioavailability (F50%):	0.977

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.661
Plasma Protein Binding (PPB):	77.846%	Volume Distribution (VD):	-0.06
Fu:	23.343% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.047
OATP1B3 inhibitor:	0.989	BCRP inhibitor:	0.597
BSEP inhibitor:	0.271

ADMET: Metabolism

CYP1A2-inhibitor:	0.458	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.997	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.833
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.0 ? 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):

2.598

Half-life (T1/2):

1.999

ADMET: Toxicity

hERG Blockers:	0.188	hERG Blockers (10um):	0.436
Human Hepatotoxicity (H-HT):	0.56	Drug-induced Liver Injury (DILI):	0.906
AMES Toxicity:	0.697	Rat Oral Acute Toxicity:	0.333
Maximum Recommended Daily Dose:	0.353	Skin Sensitization:	0.048
Carcinogencity:	0.556	Eye Corrosion:	0.0
Eye Irritation:	0.168	Respiratory Toxicity:	0.176
Drug-induced Neurotoxicity:	0.392	Ototoxicity:	0.905
Hematotoxicity:	0.15	Drug-induced Nephrotoxicity:	0.317
Genotoxicity:	0.262	RPMI-8226 Immunitoxicity:	0.091
A549 Cytotoxicity:	0.079	Hek293 Cytotoxicity:	0.489
BCF:	0.654 ? 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:	3.373 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.089 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.177 ? 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
NPO8707.1	Pueraria montana var. lobata	Varieties	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8707.1	Pueraria montana var. lobata	Varieties	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8707.1	Pueraria montana var. lobata	Varieties	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO8707.1	Pueraria montana var. lobata	Varieties	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

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 NPC198030 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	20664
0.1-0.2	25139
0.2-0.3	3016
0.3-0.4	775
0.4-0.5	200
0.5-0.6	36
0.6-0.7	15
0.7-0.8	0
0.8-0.85	3
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC45165
0.8333	Intermediate Similarity	NPC229729
0.8286	Intermediate Similarity	NPC161749
0.8261	Intermediate Similarity	NPC135345
0.7838	Intermediate Similarity	NPC601607
0.7826	Intermediate Similarity	NPC25547
0.7534	Intermediate Similarity	NPC603782
0.7297	Intermediate Similarity	NPC258035
0.72	Intermediate Similarity	NPC73511
0.6933	Remote Similarity	NPC211014
0.6842	Remote Similarity	NPC105511
0.6456	Remote Similarity	NPC100720
0.6447	Remote Similarity	NPC487214
0.641	Remote Similarity	NPC156457
0.6406	Remote Similarity	NPC182428
0.6296	Remote Similarity	NPC43761
0.625	Remote Similarity	NPC205076
0.622	Remote Similarity	NPC307518
0.6203	Remote Similarity	NPC197896
0.6203	Remote Similarity	NPC313163
0.6173	Remote Similarity	NPC479402
0.6067	Remote Similarity	NPC51326
0.6044	Remote Similarity	NPC235575
0.6	Remote Similarity	NPC234739
0.5952	Remote Similarity	NPC479407
0.5942	Remote Similarity	NPC136095
0.5783	Remote Similarity	NPC224462
0.5783	Remote Similarity	NPC479401
0.5765	Remote Similarity	NPC48773
0.5761	Remote Similarity	NPC231194
0.575	Remote Similarity	NPC160515
0.5679	Remote Similarity	NPC259070
0.5647	Remote Similarity	NPC479406
0.5616	Remote Similarity	NPC103409
0.561	Remote Similarity	NPC168822
0.561	Remote Similarity	NPC95090
0.561	Remote Similarity	NPC27408
0.5542	Remote Similarity	NPC186807
0.5541	Remote Similarity	NPC254741
0.5493	Remote Similarity	NPC181124
0.5488	Remote Similarity	NPC58053
0.5488	Remote Similarity	NPC478528
0.5476	Remote Similarity	NPC138540
0.5465	Remote Similarity	NPC607201
0.5441	Remote Similarity	NPC120924
0.5429	Remote Similarity	NPC185607
0.5412	Remote Similarity	NPC481043
0.5412	Remote Similarity	NPC80140
0.5281	Remote Similarity	NPC487212
0.5275	Remote Similarity	NPC479405
0.5275	Remote Similarity	NPC475155
0.5217	Remote Similarity	NPC479404
0.5139	Remote Similarity	NPC479067
0.5139	Remote Similarity	NPC603503
0.5119	Remote Similarity	NPC348541
0.5116	Remote Similarity	NPC182045
0.5068	Remote Similarity	NPC186507
0.5068	Remote Similarity	NPC209560
0.5068	Remote Similarity	NPC490700
0.5067	Remote Similarity	NPC602183

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC198030 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4668
0.1-0.2	4339
0.2-0.3	126
0.3-0.4	11
0.4-0.5	3
0.5-0.6	2
0.6-0.7	0
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8286	Intermediate Similarity	NPD4381	Clinical (unspecified phase)
0.5366	Remote Similarity	NPD3818	Discontinued
0.5139	Remote Similarity	NPD2796	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