NPASS Compound

Natural Product: NPC540669

Natural Product ID	NPC540669
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	4-oxo-4-[[(2~{R},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-[3-(4-hydroxyphenyl)-4-oxo-chromen-7-yl]oxy-tetrahydropyran-2-yl]methoxy]butanoic acid
IUPAC Name	4-oxo-4-[[(2~{R},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-[3-(4-hydroxyphenyl)-4-oxo-chromen-7-yl]oxy-tetrahydropyran-2-yl]methoxy]butanoic acid
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 61 64 0 0 0 0 0 0 0 0999 V2000 7.0502 2.8704 -0.4113 O 0 0 0 0 0 0 0 0 0 0 0 0 8.0722 2.2343 -0.0521 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0726 2.8698 0.6866 O 0 0 0 0 0 0 0 0 0 0 0 0 8.2755 0.8030 -0.3821 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0918 0.2836 -1.1719 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8427 0.4007 -0.4100 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8066 0.8702 0.7510 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6699 -0.0131 -0.9741 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3932 0.0119 -0.4227 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3342 -0.8307 0.8305 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0887 -0.8435 1.4164 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1090 -1.5062 0.7076 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5896 -0.6537 -0.2531 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7176 -0.2216 -0.3676 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0350 0.6431 -1.4167 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3208 1.1115 -1.5877 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3547 0.7584 -0.7442 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6326 1.2436 -0.9405 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8754 2.0319 -1.9136 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6100 0.8465 -0.0578 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9643 1.3352 -0.2316 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0212 0.4629 -0.1280 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2905 0.9863 -0.3034 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.4896 2.3421 -0.5740 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.7946 2.7591 -0.7312 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.4045 3.1901 -0.6713 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1477 2.6765 -0.4985 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2504 -0.0076 0.9621 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0169 -0.4406 1.1040 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0497 -0.0954 0.2948 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7464 -0.5745 0.4739 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6325 -2.8009 0.0686 C 0 0 2 0 0 0 0 0 0 0 0 0 0.6343 -3.7775 0.0723 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8380 -3.2333 0.8494 C 0 0 1 0 0 0 0 0 0 0 0 0 3.2753 -4.4975 0.4828 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9215 -2.2063 0.6093 C 0 0 2 0 0 0 0 0 0 0 0 0 4.9855 -2.4841 1.4514 O 0 0 0 0 0 0 0 0 0 0 0 0 9.0656 3.8967 0.7671 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2193 0.6479 -0.9381 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3050 0.2108 0.5581 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0411 0.9035 -2.0960 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2436 -0.7556 -1.5090 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0857 1.0422 -0.1150 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6984 -0.3864 -1.2105 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0144 -0.3358 1.5795 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3595 -1.8640 1.4551 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2427 0.9346 -2.0914 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5752 1.7909 -2.4103 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9070 -0.5855 0.0789 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1234 0.3144 -0.2247 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.5671 2.3604 -0.2257 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5950 4.2365 -0.8823 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2820 3.3347 -0.5727 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9917 -0.3582 1.6979 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5446 -1.2389 1.2951 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9143 -2.6412 -0.9878 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9271 -4.4787 -0.5870 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5513 -3.2006 1.9372 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6043 -5.1536 0.7989 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2182 -2.2927 -0.4737 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6197 -2.9262 2.2565 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 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 18 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 24 26 1 0 26 27 2 0 20 28 2 0 28 29 1 0 29 30 1 0 30 31 2 0 12 32 1 0 32 33 1 0 32 34 1 0 34 35 1 0 34 36 1 0 36 37 1 0 36 10 1 0 31 14 1 0 30 17 1 0 27 21 1 0 3 38 1 0 4 39 1 0 4 40 1 0 5 41 1 0 5 42 1 0 9 43 1 0 9 44 1 0 10 45 1 1 12 46 1 1 15 47 1 0 16 48 1 0 22 49 1 0 23 50 1 0 25 51 1 0 26 52 1 0 27 53 1 0 28 54 1 0 31 55 1 0 32 56 1 6 33 57 1 0 34 58 1 1 35 59 1 0 36 60 1 6 37 61 1 0 M END

Standard InCHIKey	DAAMWCXIVXEKPU-GOZZSVHWSA-N
Standard InCHI	InChI=1S/C25H24O12/c26-13-3-1-12(2-4-13)16-10-34-17-9-14(5-6-15(17)21(16)30)36-25-24(33)23(32)22(31)18(37-25)11-35-20(29)8-7-19(27)28/h1-6,9-10,18,22-26,31-33H,7-8,11H2,(H,27,28)/t18-,22-,23+,24-,25-/m1/s1
SMILES	O=C(O)CCC(=O)OC[C@H]1O[C@@H](OC2=CC=C3C(=O)C(C4=CC=C(O)C=C4)=COC3=C2)[C@H](O)[C@@H](O)[C@@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	516.13	Volume:	485.848 ? Van der Waals volume.
Dense:	1.062	LogP:	-0.284 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.802 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.417 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	26.0
TPSA:	193.19 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	5.0	Rings:	4.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.264	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.855	Fsp³:	0.32
MCE-18:	85.879 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.429	Fluc inhibitor:	0.343 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.953 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.833 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.104	Promiscuous compounds:	0.398

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.25	MDCK Permeability:	-5.131
Pgp-inhibitor:	0.0	Pgp-substrate:	0.007
PAMPA:	1.0 ? 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):	0.75
20% Bioavailability (F20%):	0.436	30% Bioavailability (F30%):	0.942
50% Bioavailability (F50%):	0.832

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.209
Plasma Protein Binding (PPB):	83.873%	Volume Distribution (VD):	-0.202
Fu:	16.313% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.0
BSEP inhibitor:	0.247

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.47	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.985
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.979
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):

1.69

Half-life (T1/2):

2.096

ADMET: Toxicity

hERG Blockers:	0.022	hERG Blockers (10um):	0.094
Human Hepatotoxicity (H-HT):	0.443	Drug-induced Liver Injury (DILI):	0.872
AMES Toxicity:	0.547	Rat Oral Acute Toxicity:	0.069
Maximum Recommended Daily Dose:	0.152	Skin Sensitization:	0.511
Carcinogencity:	0.161	Eye Corrosion:	0.0
Eye Irritation:	0.422	Respiratory Toxicity:	0.028
Drug-induced Neurotoxicity:	0.024	Ototoxicity:	0.854
Hematotoxicity:	0.193	Drug-induced Nephrotoxicity:	0.843
Genotoxicity:	0.838	RPMI-8226 Immunitoxicity:	0.122
A549 Cytotoxicity:	0.013	Hek293 Cytotoxicity:	0.077
BCF:	0.4 ? 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:	3.009 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.458 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.761 ? 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
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	PMID[11112781]
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	PMID[153409]
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	PMID[21673922]
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	PMID[23265519]
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	PMID[23317005]
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	PMID[23488669]
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	PMID[27524650]
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	PMID[29115831]
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	PMID[31287310]
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20523	Bacillus subtilis	Species	Bacillaceae	Bacteria	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 NPC540669 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	11075
0.1-0.2	34853
0.2-0.3	3120
0.3-0.4	668
0.4-0.5	115
0.5-0.6	24
0.6-0.7	4
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
0.6782	Remote Similarity	NPC211014
0.6705	Remote Similarity	NPC161749
0.6238	Remote Similarity	NPC231194
0.604	Remote Similarity	NPC51326
0.58	Remote Similarity	NPC479405
0.58	Remote Similarity	NPC303913
0.5778	Remote Similarity	NPC25547
0.5743	Remote Similarity	NPC479404
0.5714	Remote Similarity	NPC235575
0.5686	Remote Similarity	NPC64051
0.5591	Remote Similarity	NPC45165
0.5556	Remote Similarity	NPC121703
0.5408	Remote Similarity	NPC229729
0.5368	Remote Similarity	NPC259070
0.5368	Remote Similarity	NPC348541
0.5312	Remote Similarity	NPC197896
0.5312	Remote Similarity	NPC105511
0.5312	Remote Similarity	NPC258035
0.5312	Remote Similarity	NPC313163
0.5253	Remote Similarity	NPC43761
0.5253	Remote Similarity	NPC610187
0.5238	Remote Similarity	NPC46202
0.5176	Remote Similarity	NPC181124
0.514	Remote Similarity	NPC229409
0.51	Remote Similarity	NPC601607
0.5088	Remote Similarity	NPC277532
0.5051	Remote Similarity	NPC100720
0.5051	Remote Similarity	NPC205076

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC540669 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2921
0.1-0.2	6077
0.2-0.3	140
0.3-0.4	9
0.4-0.5	2
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
0.6705	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