NPASS Compound

Natural Product: NPC496489

Natural Product ID	NPC496489
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5-hydroxy-7-methoxy-2-phenyl-3-[(2~{S},3~{R},4~{S},5~{R},6~{R})-3,4,5-trihydroxy-6-[[(2~{R},3~{S},4~{S},5~{R},6~{R})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxymethyl]tetrahydropyran-2-yl]oxy-chromen-4-one
IUPAC Name	5-hydroxy-7-methoxy-2-phenyl-3-[(2~{S},3~{R},4~{S},5~{R},6~{R})-3,4,5-trihydroxy-6-[[(2~{R},3~{S},4~{S},5~{R},6~{R})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxymethyl]tetrahydropyran-2-yl]oxy-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

Standard InCHIKey	PQRFZVPEJNZXRT-ANIFWSABSA-N
Standard InCHI	InChI=1S/C28H32O14/c1-11-18(30)21(33)23(35)27(39-11)38-10-16-19(31)22(34)24(36)28(41-16)42-26-20(32)17-14(29)8-13(37-2)9-15(17)40-25(26)12-6-4-3-5-7-12/h3-9,11,16,18-19,21-24,27-31,33-36H,10H2,1-2H3/t11-,16-,18+,19+,21+,22+,23+,24-,27-,28+/m1/s1
SMILES	COC1=CC(O)=C2C(=O)C(O[C@@H]3O[C@H](CO[C@@H]4O[C@H](C)[C@H](O)[C@H](O)[C@@H]4O)[C@H](O)[C@H](O)[C@H]3O)=C(C3=CC=CC=C3)OC2=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	592.18	Volume:	552.033 ? Van der Waals volume.
Dense:	1.073	LogP:	1.502 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.835 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.444 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	30.0
TPSA:	217.97 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	7.0	Rings:	5.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.179	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.56	Fsp³:	0.464
MCE-18:	115.098 ? 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:	0.61	Fluc inhibitor:	0.247 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.646 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.597 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.044	Promiscuous compounds:	0.275

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.177	MDCK Permeability:	-5.212
Pgp-inhibitor:	0.003	Pgp-substrate:	0.872
PAMPA:	0.998 ? 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):	0.918
20% Bioavailability (F20%):	0.523	30% Bioavailability (F30%):	0.994
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.639
Plasma Protein Binding (PPB):	92.991%	Volume Distribution (VD):	-0.154
Fu:	6.219% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.879
OATP1B3 inhibitor:	0.985	BCRP inhibitor:	0.29
BSEP inhibitor:	0.008

ADMET: Metabolism

CYP1A2-inhibitor:	0.003	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.005
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.021
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.957
HLM stability:	0.872 ? 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):

1.085

Half-life (T1/2):

2.156

ADMET: Toxicity

hERG Blockers:	0.017	hERG Blockers (10um):	0.111
Human Hepatotoxicity (H-HT):	0.601	Drug-induced Liver Injury (DILI):	0.989
AMES Toxicity:	0.987	Rat Oral Acute Toxicity:	0.07
Maximum Recommended Daily Dose:	0.095	Skin Sensitization:	1.0
Carcinogencity:	0.277	Eye Corrosion:	0.0
Eye Irritation:	0.54	Respiratory Toxicity:	0.221
Drug-induced Neurotoxicity:	0.089	Ototoxicity:	0.714
Hematotoxicity:	0.778	Drug-induced Nephrotoxicity:	0.667
Genotoxicity:	0.933	RPMI-8226 Immunitoxicity:	0.234
A549 Cytotoxicity:	0.986	Hek293 Cytotoxicity:	0.873
BCF:	0.522 ? 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:	3.225 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.577 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.909 ? 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
NPO50032	Datisca cannabina	Species	Datiscaceae	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 NPC496489 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	19350
0.1-0.2	26512
0.2-0.3	3011
0.3-0.4	511
0.4-0.5	289
0.5-0.6	116
0.6-0.7	48
0.7-0.8	2
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
0.8434	Intermediate Similarity	NPC186816
0.7317	Intermediate Similarity	NPC46420
0.7253	Intermediate Similarity	NPC142142
0.7222	Intermediate Similarity	NPC470443
0.7159	Intermediate Similarity	NPC173582
0.7159	Intermediate Similarity	NPC265885
0.7159	Intermediate Similarity	NPC181465
0.7159	Intermediate Similarity	NPC215710
0.7159	Intermediate Similarity	NPC473438
0.7159	Intermediate Similarity	NPC253788
0.7108	Intermediate Similarity	NPC271692
0.7079	Intermediate Similarity	NPC22062
0.7079	Intermediate Similarity	NPC473634
0.7079	Intermediate Similarity	NPC138811
0.7	Intermediate Similarity	NPC473571
0.7	Intermediate Similarity	NPC110941
0.6988	Remote Similarity	NPC158674
0.6966	Remote Similarity	NPC67105
0.6966	Remote Similarity	NPC227508
0.6957	Remote Similarity	NPC209296
0.6957	Remote Similarity	NPC473327
0.6923	Remote Similarity	NPC126784
0.6923	Remote Similarity	NPC241423
0.6889	Remote Similarity	NPC203259
0.6889	Remote Similarity	NPC33054
0.6889	Remote Similarity	NPC210073
0.6889	Remote Similarity	NPC176740
0.6889	Remote Similarity	NPC471725
0.6889	Remote Similarity	NPC134532
0.6889	Remote Similarity	NPC602582
0.6867	Remote Similarity	NPC249281
0.6837	Remote Similarity	NPC25523
0.6809	Remote Similarity	NPC476472
0.6809	Remote Similarity	NPC294815
0.6809	Remote Similarity	NPC16194
0.6778	Remote Similarity	NPC44931
0.6778	Remote Similarity	NPC39834
0.6744	Remote Similarity	NPC611303
0.6705	Remote Similarity	NPC276377
0.6703	Remote Similarity	NPC65563
0.6703	Remote Similarity	NPC470949
0.6667	Remote Similarity	NPC480441
0.6632	Remote Similarity	NPC473073
0.6404	Remote Similarity	NPC116458
0.6404	Remote Similarity	NPC246943
0.6364	Remote Similarity	NPC121703
0.6344	Remote Similarity	NPC150164
0.6222	Remote Similarity	NPC605784
0.6211	Remote Similarity	NPC240306
0.6186	Remote Similarity	NPC486577
0.6129	Remote Similarity	NPC471079
0.6117	Remote Similarity	NPC277532
0.6105	Remote Similarity	NPC204693
0.6092	Remote Similarity	NPC289667
0.6082	Remote Similarity	NPC32641
0.6082	Remote Similarity	NPC256188
0.6082	Remote Similarity	NPC72016
0.6082	Remote Similarity	NPC606657
0.6064	Remote Similarity	NPC275454
0.6042	Remote Similarity	NPC488073
0.6023	Remote Similarity	NPC297987
0.6022	Remote Similarity	NPC251417
0.6	Remote Similarity	NPC303913
0.6	Remote Similarity	NPC156869
0.5941	Remote Similarity	NPC14187
0.5918	Remote Similarity	NPC473623
0.5918	Remote Similarity	NPC35119
0.5895	Remote Similarity	NPC67326
0.5876	Remote Similarity	NPC488074
0.5872	Remote Similarity	NPC209550
0.5859	Remote Similarity	NPC488089
0.5843	Remote Similarity	NPC136042
0.5842	Remote Similarity	NPC135358
0.5825	Remote Similarity	NPC189564
0.5816	Remote Similarity	NPC12013
0.5816	Remote Similarity	NPC11432
0.5816	Remote Similarity	NPC477613
0.5789	Remote Similarity	NPC187379
0.5778	Remote Similarity	NPC84362
0.5778	Remote Similarity	NPC27640
0.5743	Remote Similarity	NPC470449
0.5728	Remote Similarity	NPC203145
0.5728	Remote Similarity	NPC11468
0.5714	Remote Similarity	NPC103904
0.5686	Remote Similarity	NPC470446
0.5644	Remote Similarity	NPC470447
0.5625	Remote Similarity	NPC609888
0.5619	Remote Similarity	NPC292019
0.5619	Remote Similarity	NPC202908
0.5618	Remote Similarity	NPC111929
0.5618	Remote Similarity	NPC320283
0.5618	Remote Similarity	NPC41121
0.56	Remote Similarity	NPC122467
0.5588	Remote Similarity	NPC101636
0.5588	Remote Similarity	NPC221342
0.5588	Remote Similarity	NPC470445
0.5588	Remote Similarity	NPC476470
0.5579	Remote Similarity	NPC116864
0.5579	Remote Similarity	NPC244776
0.5577	Remote Similarity	NPC89052
0.5556	Remote Similarity	NPC475366
0.5556	Remote Similarity	NPC238376
0.5556	Remote Similarity	NPC153755
0.5543	Remote Similarity	NPC59534
0.5536	Remote Similarity	NPC175429
0.5534	Remote Similarity	NPC602448
0.55	Remote Similarity	NPC65711
0.5495	Remote Similarity	NPC265530
0.549	Remote Similarity	NPC89127
0.5484	Remote Similarity	NPC219904
0.5472	Remote Similarity	NPC173837
0.5446	Remote Similarity	NPC138990
0.5435	Remote Similarity	NPC305811
0.5435	Remote Similarity	NPC349108
0.5421	Remote Similarity	NPC473644
0.5417	Remote Similarity	NPC265115
0.54	Remote Similarity	NPC46202
0.54	Remote Similarity	NPC64425
0.5385	Remote Similarity	NPC127546
0.5385	Remote Similarity	NPC57625
0.5385	Remote Similarity	NPC108831
0.5385	Remote Similarity	NPC19709
0.5385	Remote Similarity	NPC173637
0.5385	Remote Similarity	NPC317489
0.5385	Remote Similarity	NPC223424
0.5385	Remote Similarity	NPC182634
0.5385	Remote Similarity	NPC600591
0.537	Remote Similarity	NPC311850
0.5368	Remote Similarity	NPC223747
0.5368	Remote Similarity	NPC99957
0.5333	Remote Similarity	NPC470455
0.5315	Remote Similarity	NPC198199
0.5312	Remote Similarity	NPC355481
0.5275	Remote Similarity	NPC473043
0.5275	Remote Similarity	NPC135599
0.5275	Remote Similarity	NPC73855
0.5275	Remote Similarity	NPC331652
0.5275	Remote Similarity	NPC113968
0.5275	Remote Similarity	NPC328940
0.5275	Remote Similarity	NPC277174
0.5275	Remote Similarity	NPC606877
0.5268	Remote Similarity	NPC474522
0.5225	Remote Similarity	NPC68592
0.5213	Remote Similarity	NPC472459
0.52	Remote Similarity	NPC479405
0.52	Remote Similarity	NPC475155
0.5196	Remote Similarity	NPC483414
0.5196	Remote Similarity	NPC483415
0.5176	Remote Similarity	NPC469622
0.5175	Remote Similarity	NPC120952
0.5169	Remote Similarity	NPC483159
0.5169	Remote Similarity	NPC483160
0.5152	Remote Similarity	NPC480466
0.5149	Remote Similarity	NPC129264
0.5149	Remote Similarity	NPC479404
0.5146	Remote Similarity	NPC483416
0.5146	Remote Similarity	NPC229409
0.5143	Remote Similarity	NPC298171
0.5138	Remote Similarity	NPC303694
0.513	Remote Similarity	NPC192539
0.5109	Remote Similarity	NPC114740
0.5106	Remote Similarity	NPC24043
0.5104	Remote Similarity	NPC181616
0.5098	Remote Similarity	NPC470125
0.5098	Remote Similarity	NPC64051
0.5094	Remote Similarity	NPC470450
0.5093	Remote Similarity	NPC470451
0.5051	Remote Similarity	NPC480463
0.5051	Remote Similarity	NPC278419
0.5051	Remote Similarity	NPC179198
0.505	Remote Similarity	NPC473512
0.505	Remote Similarity	NPC129827
0.505	Remote Similarity	NPC605592
0.5049	Remote Similarity	NPC479403
0.5048	Remote Similarity	NPC85751
0.5048	Remote Similarity	NPC475382
0.5048	Remote Similarity	NPC471669
0.5048	Remote Similarity	NPC19240
0.5043	Remote Similarity	NPC241781
0.5042	Remote Similarity	NPC473554

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC496489 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4583
0.1-0.2	4481
0.2-0.3	76
0.3-0.4	3
0.4-0.5	2
0.5-0.6	1
0.6-0.7	2
0.7-0.8	2
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
0.7753	Intermediate Similarity	NPD7251	Phase 2
0.7419	Intermediate Similarity	NPD7808	Phase 3
0.6957	Remote Similarity	NPD7054	Phase 4
0.6889	Remote Similarity	NPD6797	Phase 2
0.5577	Remote Similarity	NPD7472	Pre-clinical

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