NPASS Compound

Natural Product: NPC475084

Natural Product ID	NPC475084
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Combretastatin A-1 2'-Beta-D-Glucoside
IUPAC Name	(2R,3S,4R,5R,6S)-2-[2-hydroxy-3-methoxy-6-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenoxy]-6-(hydroxymethyl)oxane-3,4,5-triol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL496450
PubChem CID	44583740
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000253] Stilbenes [CHEMONTID:0000142] Stilbene glycosides

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 65 67 0 0 0 0 0 0 0 0999 V2000 2.1064 6.4485 2.6580 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8158 5.6781 1.5280 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2699 4.4279 1.6475 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0123 3.7319 0.4902 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4608 2.4626 0.5575 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1560 1.8702 1.7429 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4183 2.5758 2.9357 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9657 3.8293 2.8448 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5269 0.5989 1.9286 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1429 -0.0876 0.9955 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8095 -1.3637 1.2387 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4505 -1.9700 0.1582 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1112 -3.1711 0.2481 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1510 -3.8220 1.4599 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5225 -3.2381 2.5401 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8563 -2.0157 2.4280 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5864 -3.9269 3.7405 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9709 -3.3955 4.8857 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8202 -5.0447 1.5645 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0882 -6.2398 1.3108 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7418 -3.7512 -0.8476 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7236 -3.1144 -2.0995 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2456 1.8352 -0.6620 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2872 1.0991 -1.3146 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9750 -0.2463 -1.7739 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6339 -0.7073 -3.0414 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2618 0.3582 -3.8626 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8630 1.3702 -2.8824 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7479 1.9761 -2.3072 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7094 2.3339 -3.6599 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9340 2.8788 -4.6802 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2528 1.0617 -4.5537 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7583 -1.4240 -3.8646 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2733 -1.2167 -0.7844 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3150 4.3254 -0.7471 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4643 5.8832 3.5363 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8967 7.1851 2.3506 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1892 7.0176 2.9401 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1914 2.1379 3.9146 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1644 4.3727 3.7806 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5366 0.1506 2.9210 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1772 0.3230 0.0146 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4468 -1.4875 -0.8228 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3905 -1.6136 3.2902 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1470 -4.0028 5.7878 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8692 -3.3280 4.6985 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2910 -2.3604 5.1218 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3511 -6.1045 0.4913 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5479 -6.4978 2.2215 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8005 -7.0223 0.9694 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2017 -2.1026 -2.0547 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6925 -2.9655 -2.4621 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2508 -3.7282 -2.8413 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1299 1.0784 -0.5765 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1142 -0.3502 -1.9510 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4570 -1.4439 -2.7939 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9931 -0.0075 -4.5790 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4394 0.7740 -2.1522 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5415 1.7707 -4.1277 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0792 3.1098 -2.9457 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2882 2.6681 -5.5790 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3807 0.9395 -4.1047 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1317 -1.9796 -3.3509 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2453 -1.1295 -0.5695 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2644 4.5864 -0.9497 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 2 0 6 7 1 0 7 8 2 0 6 9 1 0 9 10 2 3 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 15 17 1 0 17 18 1 0 14 19 1 0 19 20 1 0 13 21 1 0 21 22 1 0 5 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 28 30 1 0 30 31 1 0 27 32 1 0 26 33 1 0 25 34 1 0 4 35 1 0 8 3 1 0 16 11 1 0 29 24 1 0 1 36 1 0 1 37 1 0 1 38 1 0 7 39 1 0 8 40 1 0 9 41 1 0 10 42 1 0 12 43 1 0 16 44 1 0 18 45 1 0 18 46 1 0 18 47 1 0 20 48 1 0 20 49 1 0 20 50 1 0 22 51 1 0 22 52 1 0 22 53 1 0 24 54 1 0 25 55 1 0 26 56 1 0 27 57 1 0 28 58 1 0 30 59 1 0 30 60 1 0 31 61 1 0 32 62 1 0 33 63 1 0 34 64 1 0 35 65 1 0 M END

Standard InCHIKey	XHGAARWVROFCOU-QQLFSGFHSA-N
Standard InCHI	InChI=1S/C24H30O11/c1-30-14-8-7-13(6-5-12-9-15(31-2)23(33-4)16(10-12)32-3)22(19(14)27)35-24-21(29)20(28)18(26)17(11-25)34-24/h5-10,17-18,20-21,24-29H,11H2,1-4H3/b6-5-/t17-,18-,20+,21-,24+/m0/s1
SMILES	COC1=C(C(=C(C=C1)C=CC2=CC(=C(C(=C2)OC)OC)OC)OC3C(C(C(C(O3)CO)O)O)O)O

Calculated Properties

Physi-Chem Properties

MedChem Properties

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

ADMET: Distribution

ADMET: Metabolism

ADMET: Excretion

ADMET: Toxicity

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO33339	combretum erythrophyllum	Species	Combretaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10785413]

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

Activity Type	# Activity
IC50	5

Activity Type	# Activity
Cell line	2
Organism	3

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
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	1.5	ug.mL-1	PMID[22916954]
NPT81	Cell line	A549	Homo sapiens	IC50	=	7.0	ug.mL-1	PMID[10843574]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	IC50	=	13.0	ug.mL-1	PMID[16038557]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	IC50	>	100.0	ug.mL-1	PMID[16038557]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	IC50	=	3.0	ug.mL-1	PMID[15974609]

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 NPC475084 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	18258
0.1-0.2	26114
0.2-0.3	4354
0.3-0.4	759
0.4-0.5	318
0.5-0.6	47
0.6-0.7	2
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
0.7188	Intermediate Similarity	NPC479030
0.6935	Remote Similarity	NPC479029
0.6716	Remote Similarity	NPC475096
0.5942	Remote Similarity	NPC604095
0.5938	Remote Similarity	NPC49074
0.5846	Remote Similarity	NPC479028
0.5846	Remote Similarity	NPC479031
0.5758	Remote Similarity	NPC210478
0.5672	Remote Similarity	NPC248355
0.5616	Remote Similarity	NPC148273
0.5606	Remote Similarity	NPC162093
0.5571	Remote Similarity	NPC294166
0.5571	Remote Similarity	NPC115022
0.5556	Remote Similarity	NPC98777
0.5522	Remote Similarity	NPC214910
0.5397	Remote Similarity	NPC299144
0.5362	Remote Similarity	NPC55040
0.5352	Remote Similarity	NPC252169
0.5342	Remote Similarity	NPC212770
0.5323	Remote Similarity	NPC192810
0.5294	Remote Similarity	NPC26080
0.5294	Remote Similarity	NPC165686
0.5286	Remote Similarity	NPC302378
0.5286	Remote Similarity	NPC59324
0.5286	Remote Similarity	NPC232673
0.527	Remote Similarity	NPC216129
0.527	Remote Similarity	NPC130449
0.527	Remote Similarity	NPC248132
0.5246	Remote Similarity	NPC276195
0.5238	Remote Similarity	NPC152722
0.5231	Remote Similarity	NPC69513
0.5217	Remote Similarity	NPC105827
0.5211	Remote Similarity	NPC470236
0.5205	Remote Similarity	NPC260681
0.5152	Remote Similarity	NPC48863
0.5152	Remote Similarity	NPC166040
0.5152	Remote Similarity	NPC251981
0.5152	Remote Similarity	NPC13745
0.5147	Remote Similarity	NPC472024
0.5147	Remote Similarity	NPC205054
0.5139	Remote Similarity	NPC242028
0.5139	Remote Similarity	NPC203230
0.5139	Remote Similarity	NPC65530
0.5075	Remote Similarity	NPC215833
0.5072	Remote Similarity	NPC481303
0.507	Remote Similarity	NPC85799
0.507	Remote Similarity	NPC303422
0.507	Remote Similarity	NPC218003
0.5068	Remote Similarity	NPC37468
0.5068	Remote Similarity	NPC8497

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC475084 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4077
0.1-0.2	4917
0.2-0.3	140
0.3-0.4	13
0.4-0.5	3
0.5-0.6	0
0.6-0.7	0
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
		NPD

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