NPASS Compound

Natural Product: NPC200316

Natural Product ID	NPC200316
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KRJPWSDKKBLTLE-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	5408543
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002506] Isoflavonoids [CHEMONTID:0002586] O-methylated isoflavonoids [CHEMONTID:0002606] 4'-O-methylated isoflavonoids [CHEMONTID:0002687] 4'-O-methylisoflavones

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 37 39 0 0 0 0 0 0 0 0999 V2000 5.8444 1.4825 0.2212 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9479 0.4475 0.5039 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6053 0.4481 0.1979 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0102 1.5170 -0.4402 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6666 1.5326 -0.7534 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9252 0.4236 -0.4006 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5214 -0.6450 0.2376 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8655 -0.6627 0.5519 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4492 -1.7544 1.1982 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6237 -2.8530 1.5268 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4907 0.3922 -0.7082 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0061 0.7791 -1.9326 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3020 0.7317 -2.1622 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1654 0.3223 -1.2601 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5174 0.2929 -1.5555 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3988 -0.1363 -0.6031 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9703 -0.5456 0.6595 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6207 -0.5118 0.9421 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7109 -0.0779 -0.0155 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3644 -0.0441 0.2662 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9443 -0.4058 1.3933 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1648 -0.9134 2.1907 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.7539 -0.1527 -0.9357 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8233 1.6756 -0.8543 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6328 2.3955 0.8340 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8595 1.1423 0.5526 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5817 2.4050 -0.7277 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2212 2.3841 -1.2552 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9206 -1.5189 0.5118 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0513 -3.2131 0.6219 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1996 -3.7225 1.8740 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8531 -2.5409 2.2768 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3139 1.1201 -2.6915 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8703 0.6118 -2.5446 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7137 -0.8759 1.3744 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0538 -0.2582 2.9666 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2412 0.7286 -0.9636 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 8 9 1 0 9 10 1 0 6 11 1 0 11 12 2 0 12 13 1 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 19 20 1 0 20 21 2 0 18 22 1 0 16 23 1 0 8 3 1 0 20 11 1 0 19 14 1 0 1 24 1 0 1 25 1 0 1 26 1 0 4 27 1 0 5 28 1 0 7 29 1 0 10 30 1 0 10 31 1 0 10 32 1 0 12 33 1 0 15 34 1 0 17 35 1 0 22 36 1 0 23 37 1 0 M END

Standard InCHIKey	KRJPWSDKKBLTLE-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C17H14O6/c1-21-13-4-3-9(5-14(13)22-2)11-8-23-15-7-10(18)6-12(19)16(15)17(11)20/h3-8,18-19H,1-2H3
SMILES	COc1ccc(cc1OC)c1coc2cc(cc(c2c1=O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	314.08	Volume:	308.569 ? Van der Waals volume.
Dense:	1.018	LogP:	2.003 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.043 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.073 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	18.0
TPSA:	89.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.772	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.255	Fsp³:	0.118
MCE-18:	18.0 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.249	Fluc inhibitor:	0.922 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.88 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.61 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.403	Promiscuous compounds:	0.829

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.098	MDCK Permeability:	-4.826
Pgp-inhibitor:	0.201	Pgp-substrate:	0.601
PAMPA:	0.15 ? 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):	0.028
20% Bioavailability (F20%):	0.227	30% Bioavailability (F30%):	0.655
50% Bioavailability (F50%):	0.974

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.008	MRP1:	0.757
Plasma Protein Binding (PPB):	97.456%	Volume Distribution (VD):	-0.083
Fu:	2.173% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.774
OATP1B3 inhibitor:	0.981	BCRP inhibitor:	0.994
BSEP inhibitor:	0.895

ADMET: Metabolism

CYP1A2-inhibitor:	0.997	CYP1A2-substrate:	0.636
CYP2C19-inhibitor:	0.02	CYP2C19-substrate:	0.267
CYP2C9-inhibitor:	0.885	CYP2C9-substrate:	0.711
CYP2D6-inhibitor:	0.998	CYP2D6-substrate:	0.987
CYP3A4-inhibitor:	0.005	CYP3A4-substrate:	0.594
CYP2B6-substrate:	0.015	CYP2C8-inhibitor:	0.996
HLM stability:	0.785 ? 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):

5.466

Half-life (T1/2):

1.351

ADMET: Toxicity

hERG Blockers:	0.146	hERG Blockers (10um):	0.534
Human Hepatotoxicity (H-HT):	0.481	Drug-induced Liver Injury (DILI):	0.848
AMES Toxicity:	0.615	Rat Oral Acute Toxicity:	0.565
Maximum Recommended Daily Dose:	0.767	Skin Sensitization:	0.356
Carcinogencity:	0.765	Eye Corrosion:	0.074
Eye Irritation:	0.984	Respiratory Toxicity:	0.833
Drug-induced Neurotoxicity:	0.256	Ototoxicity:	0.195
Hematotoxicity:	0.159	Drug-induced Nephrotoxicity:	0.191
Genotoxicity:	0.902	RPMI-8226 Immunitoxicity:	0.087
A549 Cytotoxicity:	0.209	Hek293 Cytotoxicity:	0.547
BCF:	1.014 ? 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:	3.757 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.442 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.964 ? 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
NPO40124	Erythrina schliebenii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28112509]
NPO40124	Erythrina schliebenii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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
MIC	1
EC50	1

Activity Type	# Activity
Cell line	1
Organism	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
NPT82	Cell line	MDA-MB-231	Homo sapiens	EC50	=	31800.0	nM	PMID[28112509]
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	MIC	=	101800.0	nM	PMID[28112509]

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 NPC200316 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	26788
0.1-0.2	19776
0.2-0.3	2448
0.3-0.4	594
0.4-0.5	163
0.5-0.6	48
0.6-0.7	20
0.7-0.8	0
0.8-0.85	4
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8136	Intermediate Similarity	NPC479305
0.8113	Intermediate Similarity	NPC294409
0.8113	Intermediate Similarity	NPC490701
0.8036	Intermediate Similarity	NPC104728
0.7925	Intermediate Similarity	NPC78341
0.7679	Intermediate Similarity	NPC194653
0.7636	Intermediate Similarity	NPC239363
0.7544	Intermediate Similarity	NPC254702
0.7368	Intermediate Similarity	NPC481044
0.6897	Remote Similarity	NPC12377
0.6825	Remote Similarity	NPC233918
0.678	Remote Similarity	NPC279668
0.678	Remote Similarity	NPC278323
0.6724	Remote Similarity	NPC19980
0.6667	Remote Similarity	NPC142876
0.6667	Remote Similarity	NPC39426
0.6667	Remote Similarity	NPC608554
0.661	Remote Similarity	NPC309154
0.6562	Remote Similarity	NPC268059
0.6481	Remote Similarity	NPC193792
0.6452	Remote Similarity	NPC167595
0.6429	Remote Similarity	NPC38065
0.6393	Remote Similarity	NPC483637
0.6393	Remote Similarity	NPC264550
0.6364	Remote Similarity	NPC488570
0.6212	Remote Similarity	NPC280937
0.6129	Remote Similarity	NPC45291
0.6119	Remote Similarity	NPC474052
0.6029	Remote Similarity	NPC107838
0.597	Remote Similarity	NPC128774
0.5902	Remote Similarity	NPC159103
0.5862	Remote Similarity	NPC87545
0.5862	Remote Similarity	NPC195919
0.5833	Remote Similarity	NPC116632
0.5833	Remote Similarity	NPC35763
0.5806	Remote Similarity	NPC12200
0.5806	Remote Similarity	NPC603596
0.5797	Remote Similarity	NPC482075
0.5667	Remote Similarity	NPC185607
0.5645	Remote Similarity	NPC209487
0.5616	Remote Similarity	NPC156457
0.56	Remote Similarity	NPC481043
0.5574	Remote Similarity	NPC131266
0.5574	Remote Similarity	NPC269451
0.5571	Remote Similarity	NPC74178
0.5538	Remote Similarity	NPC35544
0.5522	Remote Similarity	NPC213659
0.5522	Remote Similarity	NPC326109
0.5484	Remote Similarity	NPC303644
0.5484	Remote Similarity	NPC209560
0.5484	Remote Similarity	NPC490700
0.5397	Remote Similarity	NPC250557
0.5385	Remote Similarity	NPC114192
0.5373	Remote Similarity	NPC238279
0.5373	Remote Similarity	NPC260640
0.5373	Remote Similarity	NPC608523
0.5362	Remote Similarity	NPC475705
0.5352	Remote Similarity	NPC231763
0.5312	Remote Similarity	NPC262623
0.5278	Remote Similarity	NPC52889
0.5238	Remote Similarity	NPC245382
0.5238	Remote Similarity	NPC216769
0.5231	Remote Similarity	NPC80710
0.5231	Remote Similarity	NPC139364
0.5217	Remote Similarity	NPC249824
0.5217	Remote Similarity	NPC133400
0.5217	Remote Similarity	NPC606200
0.5152	Remote Similarity	NPC109187
0.5152	Remote Similarity	NPC476055
0.5152	Remote Similarity	NPC110086
0.5152	Remote Similarity	NPC603384
0.5139	Remote Similarity	NPC303197
0.5079	Remote Similarity	NPC10467
0.5079	Remote Similarity	NPC7013
0.5072	Remote Similarity	NPC85131
0.5072	Remote Similarity	NPC185401
0.5072	Remote Similarity	NPC232947

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC200316 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4712
0.1-0.2	4344
0.2-0.3	85
0.3-0.4	7
0.4-0.5	1
0.5-0.6	0
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
0.6667	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