NPASS Compound

Natural Product: NPC532455

Natural Product ID	NPC532455
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	AKOS040763531
IUPAC Name	3-[[(2~{R},3~{S},4~{S},5~{R},6~{S})-6-[2-(3,4-dihydroxyphenyl)-5,6-dihydroxy-4-oxo-chromen-7-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-yl]methoxy]-3-oxo-propanoic 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 7.6846 -0.9023 -1.2650 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2351 -2.0739 -1.2914 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6912 -2.9510 -2.2575 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2299 -2.5706 -0.3304 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8579 -1.4737 0.6403 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4013 -0.3518 0.5302 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9394 -1.6840 1.6358 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6018 -0.6550 2.5266 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9805 0.5572 1.8726 C 0 0 1 0 0 0 0 0 0 0 0 0 2.8300 0.1278 1.2346 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1982 1.1251 0.4877 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8639 0.8252 0.4798 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0713 0.5653 -0.4248 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3678 0.2983 0.0313 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4069 0.0174 -0.8305 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1493 0.0015 -2.1844 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8810 0.2598 -2.6838 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6267 0.2425 -4.0497 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1453 0.5407 -1.7684 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4037 0.7975 -2.2564 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1712 -0.2749 -3.0326 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9285 -0.2878 -4.2705 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4530 -0.5371 -2.5500 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6313 -0.5032 -1.1933 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9609 -0.7731 -0.6530 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1088 -0.7307 0.7276 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3020 -0.9652 1.3471 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4198 -1.2578 0.5948 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.6225 -1.4943 1.2150 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.2891 -1.3037 -0.7799 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.3957 -1.5958 -1.5687 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.0578 -1.0607 -1.4010 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6224 -0.2333 -0.4095 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3611 2.4870 1.1611 C 0 0 2 0 0 0 0 0 0 0 0 0 3.5827 3.0258 0.7623 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3615 2.2312 2.6538 C 0 0 1 0 0 0 0 0 0 0 0 0 1.2844 1.4052 2.9417 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6770 1.5540 2.9777 C 0 0 2 0 0 0 0 0 0 0 0 0 4.6478 2.5521 3.0455 O 0 0 0 0 0 0 0 0 0 0 0 0 8.2041 -2.5822 -3.0733 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5996 -3.4026 0.2769 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2897 -2.8412 -0.8528 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8946 -1.1213 3.2703 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4745 -0.3512 3.1578 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7139 1.0323 1.2079 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7378 1.1937 -0.4523 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5710 0.3106 1.0935 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6315 -0.6589 -4.5147 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5295 1.0985 -3.2224 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2208 -0.7497 -3.2763 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2343 -0.5002 1.3435 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3739 -0.9213 2.4427 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1536 -0.7055 1.5525 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.8062 -0.9231 -2.1980 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0059 -1.1076 -2.4707 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5397 3.1630 0.8493 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7605 2.8030 -0.1888 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2666 3.2135 3.1671 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5429 0.4759 3.1576 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6451 1.0667 3.9765 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2877 3.4555 3.0886 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 2 0 5 7 1 0 7 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 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 1 0 17 19 2 0 19 20 1 0 16 21 1 0 21 22 2 0 21 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 28 30 1 0 30 31 1 0 30 32 2 0 24 33 1 0 11 34 1 0 34 35 1 0 34 36 1 0 36 37 1 0 36 38 1 0 38 39 1 0 38 9 1 0 19 13 1 0 32 25 1 0 33 15 1 0 3 40 1 0 4 41 1 0 4 42 1 0 8 43 1 0 8 44 1 0 9 45 1 6 11 46 1 6 14 47 1 0 18 48 1 0 20 49 1 0 23 50 1 0 26 51 1 0 27 52 1 0 29 53 1 0 31 54 1 0 32 55 1 0 34 56 1 1 35 57 1 0 36 58 1 1 37 59 1 0 38 60 1 1 39 61 1 0 M END

Standard InCHIKey	GCZGYYNUSHMJGX-ZRKQWZGSSA-N
Standard InCHI	InChI=1S/C24H22O15/c25-9-2-1-8(3-10(9)26)12-4-11(27)18-13(37-12)5-14(19(31)21(18)33)38-24-23(35)22(34)20(32)15(39-24)7-36-17(30)6-16(28)29/h1-5,15,20,22-26,31-35H,6-7H2,(H,28,29)/t15-,20-,22+,23-,24-/m1/s1
SMILES	O=C(O)CC(=O)OC[C@H]1O[C@@H](OC2=CC3=C(C(O)=C2O)C(=O)C=C(C2=CC=C(O)C(O)=C2)O3)[C@H](O)[C@@H](O)[C@@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	550.1	Volume:	494.923 ? Van der Waals volume.
Dense:	1.111	LogP:	-0.224 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.745 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.999 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	26.0
TPSA:	253.88 ? Topological Polar Surface Area.	H-Bond Acceptor:	15.0
H-Bond Donor:	8.0	Rings:	4.0
Heavy Atoms:	15.0

MedChem Properties

QED Drug-Likeness Score:	0.105	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.24	Fsp³:	0.292
MCE-18:	96.355 ? 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:	1	PAINS Alert:	1
Colloidal aggregators:	0.488	Fluc inhibitor:	0.311 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.973 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.798 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.087	Promiscuous compounds:	0.733

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.665	MDCK Permeability:	-5.139
Pgp-inhibitor:	0.0	Pgp-substrate:	0.018
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):	0.053
20% Bioavailability (F20%):	0.632	30% Bioavailability (F30%):	0.969
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.698
Plasma Protein Binding (PPB):	80.345%	Volume Distribution (VD):	-0.05
Fu:	17.067% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.105
BSEP inhibitor:	0.001

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.017
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):

1.986

Half-life (T1/2):

3.685

ADMET: Toxicity

hERG Blockers:	0.004	hERG Blockers (10um):	0.049
Human Hepatotoxicity (H-HT):	0.348	Drug-induced Liver Injury (DILI):	0.973
AMES Toxicity:	0.522	Rat Oral Acute Toxicity:	0.102
Maximum Recommended Daily Dose:	0.116	Skin Sensitization:	0.994
Carcinogencity:	0.078	Eye Corrosion:	0.0
Eye Irritation:	0.81	Respiratory Toxicity:	0.026
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.852
Hematotoxicity:	0.12	Drug-induced Nephrotoxicity:	0.493
Genotoxicity:	0.975	RPMI-8226 Immunitoxicity:	0.042
A549 Cytotoxicity:	0.122	Hek293 Cytotoxicity:	0.038
BCF:	0.313 ? 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:	2.807 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.259 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.657 ? 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
NPO44865	Bryum capillare	Species	Bryaceae	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

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 NPC532455 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	18905
0.1-0.2	28044
0.2-0.3	2077
0.3-0.4	575
0.4-0.5	207
0.5-0.6	40
0.6-0.7	7
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	Natural Product ID
0.809	Intermediate Similarity	NPC229409
0.7283	Intermediate Similarity	NPC64051
0.6915	Remote Similarity	NPC46202
0.6897	Remote Similarity	NPC58716
0.6559	Remote Similarity	NPC254540
0.6304	Remote Similarity	NPC43211
0.6222	Remote Similarity	NPC146792
0.6105	Remote Similarity	NPC477848
0.6022	Remote Similarity	NPC237435
0.5962	Remote Similarity	NPC603856
0.5938	Remote Similarity	NPC172807
0.5934	Remote Similarity	NPC45618
0.5859	Remote Similarity	NPC210073
0.5859	Remote Similarity	NPC3583
0.5686	Remote Similarity	NPC470443
0.5686	Remote Similarity	NPC65711
0.567	Remote Similarity	NPC190003
0.5638	Remote Similarity	NPC245014
0.5625	Remote Similarity	NPC115760
0.5612	Remote Similarity	NPC211594
0.5577	Remote Similarity	NPC479766
0.5463	Remote Similarity	NPC599948
0.5429	Remote Similarity	NPC270675
0.5429	Remote Similarity	NPC195685
0.5426	Remote Similarity	NPC19709
0.5377	Remote Similarity	NPC479765
0.5368	Remote Similarity	NPC189142
0.5368	Remote Similarity	NPC77660
0.5361	Remote Similarity	NPC20505
0.5321	Remote Similarity	NPC121703
0.5312	Remote Similarity	NPC45638
0.53	Remote Similarity	NPC116864
0.53	Remote Similarity	NPC244776
0.5294	Remote Similarity	NPC44931
0.5278	Remote Similarity	NPC472994
0.5258	Remote Similarity	NPC201292
0.5243	Remote Similarity	NPC233994
0.5238	Remote Similarity	NPC162313
0.5225	Remote Similarity	NPC472993
0.5189	Remote Similarity	NPC209296
0.5185	Remote Similarity	NPC298171
0.5096	Remote Similarity	NPC22062
0.5096	Remote Similarity	NPC473634
0.5096	Remote Similarity	NPC138811
0.5094	Remote Similarity	NPC211532
0.5094	Remote Similarity	NPC488364
0.5052	Remote Similarity	NPC168822
0.5048	Remote Similarity	NPC204693
0.5046	Remote Similarity	NPC101636

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC532455 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4095
0.1-0.2	4976
0.2-0.3	70
0.3-0.4	3
0.4-0.5	4
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
0.6022	Remote Similarity	NPD4338	Clinical (unspecified phase)
0.5189	Remote Similarity	NPD7054	Phase 4

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