NPASS Compound

Natural Product: NPC138540

Natural Product ID	NPC138540
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	DXPDVKIQWQRRGG-CMWLGVBASA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	101049550
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 0.2251 1.1245 1.8532 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5716 1.0150 1.5768 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9958 0.4896 0.3685 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4025 0.3361 -0.0002 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1215 1.3171 -0.6516 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3748 1.1449 -0.9654 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0647 0.0600 -0.7059 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4008 -0.0641 -1.0665 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1105 -1.2122 -0.7857 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4495 -2.2313 -0.1360 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1239 -2.0963 0.2163 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3997 -0.9649 -0.0523 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0764 -0.8390 0.3034 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4725 -1.7618 0.8932 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4481 -3.1376 0.8800 O 0 0 0 0 0 0 0 0 0 0 0 0 9.4327 -1.2970 -1.1584 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0420 0.0859 -0.5364 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3182 0.2045 -0.2392 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7635 0.7237 0.9563 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0648 0.8737 1.3253 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2309 0.5618 0.6493 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.9642 -0.5067 1.3901 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.4326 -0.5672 1.2071 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.0599 0.6743 0.6093 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.0869 1.1984 -0.4132 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.6827 2.2170 -1.3362 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7507 1.6108 -1.9934 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0002 1.6791 0.3218 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.3004 0.3444 0.0740 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0382 -0.8939 2.4241 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4212 -1.7468 0.9687 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4562 -0.4493 -1.7682 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0914 1.5390 2.8058 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3428 1.3252 2.2723 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5919 2.2527 -0.8957 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8938 0.7535 -1.5773 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9854 -3.1388 0.0935 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7817 -3.6827 0.3456 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0015 -0.4669 -1.2973 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0330 -0.1170 -0.9611 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9434 0.1329 -0.3530 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7215 -0.4976 2.4922 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6686 -1.3891 0.4685 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1698 1.4309 1.4332 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7319 0.3097 -1.0005 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0154 3.1137 -0.8198 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9286 2.4462 -2.1413 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5956 0.6485 -2.1801 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8439 1.1891 0.1136 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9174 -1.3357 2.2411 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9921 -2.4767 1.2716 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0013 0.0706 -2.4277 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 11 15 1 0 9 16 1 0 3 17 2 0 17 18 1 0 18 19 2 0 19 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 17 32 1 0 19 1 1 0 28 21 1 0 13 4 1 0 12 7 1 0 1 33 1 0 2 34 1 0 5 35 1 0 8 36 1 0 10 37 1 0 15 38 1 0 16 39 1 0 18 40 1 0 21 41 1 6 22 42 1 1 23 43 1 6 24 44 1 1 25 45 1 6 26 46 1 0 26 47 1 0 27 48 1 0 29 49 1 0 30 50 1 0 31 51 1 0 32 52 1 0 M END

Standard InCHIKey	DXPDVKIQWQRRGG-CMWLGVBASA-N
Standard InCHI	InChI=1S/C21H20O11/c22-6-15-18(27)19(28)20(29)21(32-15)31-9-1-2-10(12(24)5-9)11-7-30-14-4-8(23)3-13(25)16(14)17(11)26/h1-5,7,15,18-25,27-29H,6H2/t15-,18-,19+,20-,21-/m1/s1
SMILES	c1cc(c2coc3cc(cc(c3c2=O)O)O)c(cc1O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	448.1	Volume:	413.147 ? Van der Waals volume.
Dense:	1.085	LogP:	0.705 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.231 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.323 ? 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:	0.279	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.001	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:	0	PAINS Alert:	0
Colloidal aggregators:	0.581	Fluc inhibitor:	0.31 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.838 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.698 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.293	Promiscuous compounds:	0.517

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.355	MDCK Permeability:	-5.071
Pgp-inhibitor:	0.0	Pgp-substrate:	0.372
PAMPA:	0.982 ? 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):	0.298
20% Bioavailability (F20%):	0.267	30% Bioavailability (F30%):	0.995
50% Bioavailability (F50%):	0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.005	MRP1:	0.087
Plasma Protein Binding (PPB):	85.74%	Volume Distribution (VD):	-0.151
Fu:	12.404% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.734
BSEP inhibitor:	0.001

ADMET: Metabolism

CYP1A2-inhibitor:	0.328	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.011	CYP2C9-substrate:	0.004
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.007
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.002
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.709
HLM stability:	0.019 ? 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):

2.018

Half-life (T1/2):

4.023

ADMET: Toxicity

hERG Blockers:	0.026	hERG Blockers (10um):	0.129
Human Hepatotoxicity (H-HT):	0.676	Drug-induced Liver Injury (DILI):	0.971
AMES Toxicity:	0.922	Rat Oral Acute Toxicity:	0.077
Maximum Recommended Daily Dose:	0.15	Skin Sensitization:	0.983
Carcinogencity:	0.298	Eye Corrosion:	0.0
Eye Irritation:	0.636	Respiratory Toxicity:	0.108
Drug-induced Neurotoxicity:	0.004	Ototoxicity:	0.845
Hematotoxicity:	0.101	Drug-induced Nephrotoxicity:	0.55
Genotoxicity:	0.982	RPMI-8226 Immunitoxicity:	0.125
A549 Cytotoxicity:	0.541	Hek293 Cytotoxicity:	0.56
BCF:	0.409 ? 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:	2.954 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.339 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.559 ? 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
NPO16444	Apios americana	Species	Fabaceae	Eukaryota	Tubers	n.a.	n.a.	PMID[29932657]
NPO16444	Apios americana	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
IC50	1

Activity Type	# Activity
Cell line	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
NPT113	Cell line	RAW264.7	Mus musculus	IC50	>	1000.0	nM	PMID[29932657]

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 NPC138540 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	18643
0.1-0.2	27414
0.2-0.3	2578
0.3-0.4	878
0.4-0.5	261
0.5-0.6	62
0.6-0.7	12
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8333	Intermediate Similarity	NPC156457
0.8082	Intermediate Similarity	NPC234739
0.7532	Intermediate Similarity	NPC479401
0.7308	Intermediate Similarity	NPC80140
0.7089	Intermediate Similarity	NPC481043
0.6875	Remote Similarity	NPC479402
0.6714	Remote Similarity	NPC279668
0.6625	Remote Similarity	NPC73511
0.6533	Remote Similarity	NPC78697
0.65	Remote Similarity	NPC197896
0.65	Remote Similarity	NPC313163
0.6375	Remote Similarity	NPC143851
0.6296	Remote Similarity	NPC64305
0.6296	Remote Similarity	NPC258035
0.6222	Remote Similarity	NPC479403
0.6145	Remote Similarity	NPC472459
0.6118	Remote Similarity	NPC479406
0.5833	Remote Similarity	NPC100818
0.5765	Remote Similarity	NPC21100
0.5714	Remote Similarity	NPC161749
0.5698	Remote Similarity	NPC191306
0.5698	Remote Similarity	NPC60735
0.5698	Remote Similarity	NPC26230
0.5663	Remote Similarity	NPC160515
0.5632	Remote Similarity	NPC120099
0.5632	Remote Similarity	NPC609478
0.5595	Remote Similarity	NPC77672
0.5595	Remote Similarity	NPC133671
0.5595	Remote Similarity	NPC135391
0.5595	Remote Similarity	NPC78263
0.5595	Remote Similarity	NPC250069
0.5581	Remote Similarity	NPC205076
0.5568	Remote Similarity	NPC88023
0.5568	Remote Similarity	NPC309025
0.5543	Remote Similarity	NPC479405
0.5529	Remote Similarity	NPC145038
0.5529	Remote Similarity	NPC56077
0.5529	Remote Similarity	NPC281131
0.5529	Remote Similarity	NPC253662
0.5529	Remote Similarity	NPC179950
0.5529	Remote Similarity	NPC88789
0.5529	Remote Similarity	NPC491374
0.5484	Remote Similarity	NPC479404
0.5476	Remote Similarity	NPC45165
0.5476	Remote Similarity	NPC135345
0.5412	Remote Similarity	NPC112755
0.5412	Remote Similarity	NPC19388
0.5412	Remote Similarity	NPC170675
0.5412	Remote Similarity	NPC240431
0.5412	Remote Similarity	NPC55786
0.5412	Remote Similarity	NPC348541
0.5405	Remote Similarity	NPC294409
0.5405	Remote Similarity	NPC490701
0.5402	Remote Similarity	NPC100720
0.5393	Remote Similarity	NPC307518
0.5375	Remote Similarity	NPC268668
0.5349	Remote Similarity	NPC105511
0.5325	Remote Similarity	NPC45291
0.5281	Remote Similarity	NPC229729
0.5281	Remote Similarity	NPC197285
0.5281	Remote Similarity	NPC601710
0.5278	Remote Similarity	NPC87545
0.5233	Remote Similarity	NPC289667
0.5227	Remote Similarity	NPC325555
0.5227	Remote Similarity	NPC226304
0.5222	Remote Similarity	NPC136761
0.5204	Remote Similarity	NPC76831
0.5195	Remote Similarity	NPC278323
0.5172	Remote Similarity	NPC95090
0.5172	Remote Similarity	NPC27408
0.5172	Remote Similarity	NPC603782
0.5169	Remote Similarity	NPC307938
0.5169	Remote Similarity	NPC224462
0.5165	Remote Similarity	NPC203050
0.5165	Remote Similarity	NPC225434
0.5165	Remote Similarity	NPC48773
0.5057	Remote Similarity	NPC254306
0.5055	Remote Similarity	NPC607201
0.5054	Remote Similarity	NPC487212

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC138540 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4956
0.1-0.2	4115
0.2-0.3	63
0.3-0.4	10
0.4-0.5	5
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
0.5714	Remote Similarity	NPD4381	Clinical (unspecified phase)

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