NPASS Compound

Natural Product: NPC567805

Natural Product ID	NPC567805
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	[(2~{R},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-[(2~{R})-5-hydroxy-2-(4-hydroxy-3-methoxy-phenyl)-4-oxo-chroman-7-yl]oxy-tetrahydropyran-2-yl]methyl acetate
IUPAC Name	[(2~{R},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-[(2~{R})-5-hydroxy-2-(4-hydroxy-3-methoxy-phenyl)-4-oxo-chroman-7-yl]oxy-tetrahydropyran-2-yl]methyl acetate
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 62 65 0 0 0 0 0 0 0 0999 V2000 9.1432 -1.0803 -1.3887 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0645 -0.5234 -0.1006 O 0 0 0 0 0 0 0 0 0 0 0 0 7.8795 -0.0835 0.4684 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6504 -0.1548 -0.1911 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4908 0.2744 0.3623 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2157 0.1841 -0.3655 C 0 0 1 0 0 0 0 0 0 0 0 0 4.2921 -0.5996 -1.6378 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9943 -0.4516 -2.3416 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8568 -0.3440 -3.5807 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7707 -0.4289 -1.5236 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5492 -0.4733 -2.1544 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4624 -0.5383 -3.5427 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5901 -0.4512 -1.3607 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5234 -0.3872 0.0122 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6128 -0.3628 0.8407 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9268 -0.3901 0.4419 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.6213 0.7456 0.8595 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9107 0.8250 0.3120 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.4821 2.1834 0.4754 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7614 2.4534 0.0597 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.9761 2.1057 0.5467 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2647 2.5022 -0.1021 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0628 1.4204 1.5872 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7696 -0.3560 0.5555 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.8446 -0.4100 -0.3774 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9899 -1.6372 0.2371 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.7628 -2.7522 0.4744 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6613 -1.6462 0.9153 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9747 -2.7830 0.4941 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7616 -0.3443 0.5917 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8907 -0.3641 -0.1500 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1760 -0.3215 0.4259 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5260 0.8054 1.6338 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7451 0.8893 2.3191 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9180 0.4478 1.7418 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1052 0.5502 2.4579 O 0 0 0 0 0 0 0 0 0 0 0 0 8.6436 -0.3855 -2.0983 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6937 -2.0942 -1.4271 H 0 0 0 0 0 0 0 0 0 0 0 0 10.2210 -1.0927 -1.6667 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6784 -0.5742 -1.1706 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9281 1.2353 -0.6723 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0638 -0.2182 -2.3393 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4506 -1.6864 -1.4655 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3185 0.2579 -4.1281 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5538 -0.4875 -1.8779 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0177 -0.4080 -0.6533 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6709 0.7607 -0.8248 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8150 2.9708 0.0118 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4456 2.5017 1.5816 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4916 3.5447 0.2684 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2046 2.4601 -1.2015 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1024 1.8545 0.2168 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1879 -0.4295 1.5685 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3820 -0.3923 -1.2710 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8047 -1.5938 -0.8620 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1343 -3.1471 -0.3708 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7279 -1.6900 2.0153 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0513 -3.5319 1.1127 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8387 -0.2932 1.6797 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6327 1.1616 2.1203 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8085 1.2999 3.3167 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5552 1.4740 2.4627 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 2 0 11 12 1 0 11 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 21 23 2 0 18 24 1 0 24 25 1 0 24 26 1 0 26 27 1 0 26 28 1 0 28 29 1 0 14 30 1 0 30 31 2 0 31 32 1 0 5 33 2 0 33 34 1 0 34 35 2 0 35 36 1 0 35 3 1 0 32 6 1 0 31 10 1 0 28 16 1 0 1 37 1 0 1 38 1 0 1 39 1 0 4 40 1 0 6 41 1 6 7 42 1 0 7 43 1 0 12 44 1 0 13 45 1 0 16 46 1 6 18 47 1 6 19 48 1 0 19 49 1 0 22 50 1 0 22 51 1 0 22 52 1 0 24 53 1 1 25 54 1 0 26 55 1 6 27 56 1 0 28 57 1 1 29 58 1 0 30 59 1 0 33 60 1 0 34 61 1 0 36 62 1 0 M END

Standard InCHIKey	GPCKIXOOCSOBEC-RKJKNZIMSA-N
Standard InCHI	InChI=1S/C24H26O12/c1-10(25)33-9-19-21(29)22(30)23(31)24(36-19)34-12-6-14(27)20-15(28)8-16(35-18(20)7-12)11-3-4-13(26)17(5-11)32-2/h3-7,16,19,21-24,26-27,29-31H,8-9H2,1-2H3/t16-,19-,21-,22+,23-,24-/m1/s1
SMILES	COC1=CC([C@H]2CC(=O)C3=C(O)C=C(O[C@@H]4O[C@H](COC(C)=O)[C@@H](O)[C@H](O)[C@H]4O)C=C3O2)=CC=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	506.14	Volume:	473.825 ? Van der Waals volume.
Dense:	1.068	LogP:	1.044 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.431 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.3 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	25.0
TPSA:	181.44 ? 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:	0.344	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.139	Fsp³:	0.417
MCE-18:	92.118 ? 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:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.623	Fluc inhibitor:	0.444 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.229 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.728 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.069	Promiscuous compounds:	0.332

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.173	MDCK Permeability:	-5.163
Pgp-inhibitor:	0.934	Pgp-substrate:	0.015
PAMPA:	0.803 ? 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):	0.217
20% Bioavailability (F20%):	0.003	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.132
Plasma Protein Binding (PPB):	90.938%	Volume Distribution (VD):	-0.318
Fu:	7.602% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.981
BSEP inhibitor:	0.948

ADMET: Metabolism

CYP1A2-inhibitor:	0.02	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:	0.058
CYP3A4-inhibitor:	0.002	CYP3A4-substrate:	0.049
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.589
HLM stability:	0.137 ? 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):

2.712

Half-life (T1/2):

3.115

ADMET: Toxicity

hERG Blockers:	0.025	hERG Blockers (10um):	0.158
Human Hepatotoxicity (H-HT):	0.686	Drug-induced Liver Injury (DILI):	0.95
AMES Toxicity:	0.974	Rat Oral Acute Toxicity:	0.071
Maximum Recommended Daily Dose:	0.061	Skin Sensitization:	0.99
Carcinogencity:	0.439	Eye Corrosion:	0.0
Eye Irritation:	0.291	Respiratory Toxicity:	0.008
Drug-induced Neurotoxicity:	0.028	Ototoxicity:	0.874
Hematotoxicity:	0.428	Drug-induced Nephrotoxicity:	0.935
Genotoxicity:	0.952	RPMI-8226 Immunitoxicity:	0.223
A549 Cytotoxicity:	0.456	Hek293 Cytotoxicity:	0.39
BCF:	0.402 ? 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:	3.04 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.464 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.804 ? 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
NPO23218	Viscum coloratum	Species	Viscaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[2082684]
NPO23218	Viscum coloratum	Species	Viscaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[21922656]
NPO23218	Viscum coloratum	Species	Viscaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[3254039]
NPO23218	Viscum coloratum	Species	Viscaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[3256207]
NPO23218	Viscum coloratum	Species	Viscaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23218	Viscum coloratum	Species	Viscaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23218	Viscum coloratum	Species	Viscaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23218	Viscum coloratum	Species	Viscaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO23218	Viscum coloratum	Species	Viscaceae	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

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 NPC567805 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	12278
0.1-0.2	31496
0.2-0.3	4990
0.3-0.4	936
0.4-0.5	124
0.5-0.6	21
0.6-0.7	7
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	Natural Product ID
0.7692	Intermediate Similarity	NPC236934
0.7093	Intermediate Similarity	NPC44328
0.7093	Intermediate Similarity	NPC79056
0.7011	Intermediate Similarity	NPC293629
0.6941	Remote Similarity	NPC271270
0.6782	Remote Similarity	NPC43587
0.6778	Remote Similarity	NPC67134
0.622	Remote Similarity	NPC219163
0.622	Remote Similarity	NPC39351
0.6071	Remote Similarity	NPC29830
0.6	Remote Similarity	NPC472386
0.5904	Remote Similarity	NPC97052
0.5895	Remote Similarity	NPC261254
0.5698	Remote Similarity	NPC43638
0.56	Remote Similarity	NPC241196
0.5426	Remote Similarity	NPC472876
0.5287	Remote Similarity	NPC311803
0.5258	Remote Similarity	NPC105095
0.5258	Remote Similarity	NPC177731
0.5258	Remote Similarity	NPC725
0.519	Remote Similarity	NPC236637
0.5165	Remote Similarity	NPC194095
0.5122	Remote Similarity	NPC477840
0.5104	Remote Similarity	NPC97285
0.5104	Remote Similarity	NPC142860
0.5104	Remote Similarity	NPC152538
0.5104	Remote Similarity	NPC246469
0.5104	Remote Similarity	NPC89088
0.5056	Remote Similarity	NPC206378
0.5054	Remote Similarity	NPC472382
0.5053	Remote Similarity	NPC105283
0.5052	Remote Similarity	NPC241016

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC567805 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3713
0.1-0.2	5270
0.2-0.3	154
0.3-0.4	12
0.4-0.5	0
0.5-0.6	0
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
0.7093	Intermediate Similarity	NPD7074	Phase 3

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