NPASS Compound

Natural Product: NPC514050

Natural Product ID	NPC514050
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-6-[[(2~{R},3~{S},4~{S})-3,4-dihydroxy-4-(hydroxymethyl)tetrahydrofuran-2-yl]oxymethyl]-3,4,5-trihydroxy-tetrahydropyran-2-yl]oxy-3-(4-hydroxyphenyl)chromen-4-one
IUPAC Name	7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-6-[[(2~{R},3~{S},4~{S})-3,4-dihydroxy-4-(hydroxymethyl)tetrahydrofuran-2-yl]oxymethyl]-3,4,5-trihydroxy-tetrahydropyran-2-yl]oxy-3-(4-hydroxyphenyl)chromen-4-one
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 67 71 0 0 0 0 0 0 0 0999 V2000 5.7837 -0.0318 1.5423 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2750 -0.5609 0.5388 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9699 -1.4928 -0.2100 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3220 -1.8782 0.1675 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7398 -3.1923 0.1770 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0227 -3.5122 0.5422 C 0 0 0 0 0 0 0 0 0 0 0 0 9.9408 -2.5442 0.9117 C 0 0 0 0 0 0 0 0 0 0 0 0 11.2208 -2.9132 1.2718 O 0 0 0 0 0 0 0 0 0 0 0 0 9.5356 -1.2409 0.9050 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2426 -0.9195 0.5369 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3138 -2.0182 -1.3032 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0940 -1.6594 -1.6243 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4119 -0.7687 -0.9201 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1472 -0.4068 -1.2656 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3940 0.5299 -0.5480 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1281 0.8761 -0.9137 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7635 1.7586 -0.3623 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.9397 1.1176 0.1118 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7721 1.9822 0.7587 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.1925 1.7853 0.2072 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6170 0.4767 0.4259 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9031 0.3721 -0.1003 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.7507 0.0670 0.9573 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.8747 -1.2898 1.0578 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2536 -1.9394 -0.1348 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.0464 -2.5545 0.1154 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.2272 -2.9414 -0.7117 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4563 -2.3569 -0.9780 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0122 -0.7808 -1.0758 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.8479 -0.9462 -1.8154 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4711 3.4302 0.6738 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7565 3.7622 1.8527 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7941 3.9304 -0.5403 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.6148 4.7899 -1.2675 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3220 2.7641 -1.3712 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3692 3.1243 -2.3091 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9869 1.0905 0.5490 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2870 0.7441 0.9374 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9836 -0.1852 0.1933 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0125 -3.9284 -0.1132 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3435 -4.5618 0.5469 H 0 0 0 0 0 0 0 0 0 0 0 0 11.8381 -3.4903 0.7501 H 0 0 0 0 0 0 0 0 0 0 0 0 10.2600 -0.4953 1.1956 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9336 0.1297 0.5374 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8766 -2.7517 -1.8826 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6965 -0.8483 -2.1193 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3724 2.2987 0.5206 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8642 1.6251 1.8279 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8307 2.4535 0.8349 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3019 2.1294 -0.8221 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2710 1.3008 -0.5513 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4481 -1.7275 1.9713 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9789 -1.5212 1.1002 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9108 -2.7681 1.0804 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7857 -3.4507 -1.6030 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3749 -3.7283 0.0575 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1806 -2.8529 -0.5450 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9086 -0.6078 -1.7013 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0491 -0.5471 -1.3845 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4367 4.0072 0.7860 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3783 3.8390 2.6192 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8701 4.4906 -0.1987 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2800 5.7150 -1.1525 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1902 2.3560 -1.9224 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4644 3.4491 -1.9227 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4617 1.8169 1.1431 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7306 1.2007 1.8054 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 2 0 7 8 1 0 7 9 1 0 9 10 2 0 3 11 2 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 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 1 25 27 1 0 27 28 1 0 25 29 1 0 29 30 1 0 19 31 1 0 31 32 1 0 31 33 1 0 33 34 1 0 33 35 1 0 35 36 1 0 15 37 2 0 37 38 1 0 38 39 2 0 39 2 1 0 10 4 1 0 39 13 1 0 35 17 1 0 29 22 1 0 5 40 1 0 6 41 1 0 8 42 1 0 9 43 1 0 10 44 1 0 11 45 1 0 14 46 1 0 17 47 1 1 19 48 1 1 20 49 1 0 20 50 1 0 22 51 1 6 24 52 1 0 24 53 1 0 26 54 1 0 27 55 1 0 27 56 1 0 28 57 1 0 29 58 1 6 30 59 1 0 31 60 1 1 32 61 1 0 33 62 1 1 34 63 1 0 35 64 1 6 36 65 1 0 37 66 1 0 38 67 1 0 M END

Standard InCHIKey	VXFVOLUPWBOJSY-OZMXGZQASA-N
Standard InCHI	InChI=1S/C26H28O13/c27-10-26(34)11-37-25(23(26)33)36-9-18-20(30)21(31)22(32)24(39-18)38-14-5-6-15-17(7-14)35-8-16(19(15)29)12-1-3-13(28)4-2-12/h1-8,18,20-25,27-28,30-34H,9-11H2/t18-,20-,21+,22-,23-,24-,25-,26+/m1/s1
SMILES	O=C1C(C2=CC=C(O)C=C2)=COC2=CC(O[C@@H]3O[C@H](CO[C@@H]4OC[C@@](O)(CO)[C@@H]4O)[C@@H](O)[C@H](O)[C@H]3O)=CC=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	548.15	Volume:	508.651 ? Van der Waals volume.
Dense:	1.078	LogP:	0.853 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.209 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.313 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	29.0
TPSA:	208.74 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	7.0	Rings:	5.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.185	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.519	Fsp³:	0.423
MCE-18:	111.568 ? 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:	0.54	Fluc inhibitor:	0.286 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.912 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.392 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.123	Promiscuous compounds:	0.315

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.487	MDCK Permeability:	-5.201
Pgp-inhibitor:	0.0	Pgp-substrate:	0.218
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):	0.961
20% Bioavailability (F20%):	0.836	30% Bioavailability (F30%):	0.995
50% Bioavailability (F50%):	0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.135
Plasma Protein Binding (PPB):	78.806%	Volume Distribution (VD):	-0.257
Fu:	24.247% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.021
BSEP inhibitor:	0.002

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.003	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.994
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.976
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):

1.924

Half-life (T1/2):

3.071

ADMET: Toxicity

hERG Blockers:	0.034	hERG Blockers (10um):	0.108
Human Hepatotoxicity (H-HT):	0.712	Drug-induced Liver Injury (DILI):	0.838
AMES Toxicity:	0.962	Rat Oral Acute Toxicity:	0.038
Maximum Recommended Daily Dose:	0.07	Skin Sensitization:	0.988
Carcinogencity:	0.246	Eye Corrosion:	0.0
Eye Irritation:	0.251	Respiratory Toxicity:	0.005
Drug-induced Neurotoxicity:	0.046	Ototoxicity:	0.937
Hematotoxicity:	0.268	Drug-induced Nephrotoxicity:	0.86
Genotoxicity:	0.768	RPMI-8226 Immunitoxicity:	0.132
A549 Cytotoxicity:	0.444	Hek293 Cytotoxicity:	0.477
BCF:	0.46 ? 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:	3.158 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.705 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.838 ? 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
NPO54916	Neorautanenia amboensis	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

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 NPC514050 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	18011
0.1-0.2	28161
0.2-0.3	2824
0.3-0.4	673
0.4-0.5	160
0.5-0.6	19
0.6-0.7	7
0.7-0.8	1
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
0.8202	Intermediate Similarity	NPC235575
0.7143	Intermediate Similarity	NPC161749
0.7128	Intermediate Similarity	NPC231194
0.7024	Intermediate Similarity	NPC211014
0.6915	Remote Similarity	NPC51326
0.6667	Remote Similarity	NPC479405
0.6596	Remote Similarity	NPC479404
0.6489	Remote Similarity	NPC303913
0.625	Remote Similarity	NPC476442
0.625	Remote Similarity	NPC215512
0.6224	Remote Similarity	NPC257714
0.5977	Remote Similarity	NPC25547
0.5955	Remote Similarity	NPC45165
0.5745	Remote Similarity	NPC229729
0.5652	Remote Similarity	NPC197896
0.5652	Remote Similarity	NPC105511
0.5652	Remote Similarity	NPC313163
0.5644	Remote Similarity	NPC65711
0.5644	Remote Similarity	NPC479403
0.5543	Remote Similarity	NPC259070
0.5543	Remote Similarity	NPC348541
0.5534	Remote Similarity	NPC600130
0.5484	Remote Similarity	NPC258035
0.5417	Remote Similarity	NPC601607
0.5368	Remote Similarity	NPC100720
0.5366	Remote Similarity	NPC181124
0.5258	Remote Similarity	NPC43761
0.5208	Remote Similarity	NPC205076
0.5196	Remote Similarity	NPC475155
0.5104	Remote Similarity	NPC73511

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC514050 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4728
0.1-0.2	4349
0.2-0.3	61
0.3-0.4	5
0.4-0.5	5
0.5-0.6	1
0.6-0.7	0
0.7-0.8	1
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
0.7143	Intermediate Similarity	NPD4381	Clinical (unspecified phase)
0.5269	Remote Similarity	NPD3818	Discontinued

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