NPASS Compound

Natural Product: NPC475096

Natural Product ID	NPC475096
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Combretastatin B-1 2'-Beta-D-Glucoside
IUPAC Name	(2R,3S,4R,5R,6S)-2-[2-hydroxy-3-methoxy-6-[2-(3,4,5-trimethoxyphenyl)ethyl]phenoxy]-6-(hydroxymethyl)oxane-3,4,5-triol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL497532
PubChem CID	44583744
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 67 69 0 0 0 0 0 0 0 0999 V2000 -2.3322 -4.0005 0.2333 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5217 -2.8456 0.1554 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9769 -2.0945 -1.0843 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.2572 -0.9736 -1.2540 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8537 0.2282 -1.4688 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2280 0.7446 -0.2467 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9111 1.8058 0.5032 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8664 1.7899 1.4035 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0857 0.6552 1.5777 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1718 0.8635 0.5436 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2406 -0.1343 0.5579 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3424 -0.0051 1.4128 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3865 -0.8998 1.4383 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4433 -0.6965 2.3197 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4039 0.4304 3.1631 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3490 -1.9777 0.5808 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2807 -2.1477 -0.2824 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2365 -1.2226 -0.2837 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2126 -3.2135 -1.1556 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1277 -3.3709 -2.0340 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3601 -2.9176 0.5486 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4894 -2.8190 -0.2921 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5502 2.9056 2.1971 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2934 4.0564 2.0824 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3321 4.0499 1.1732 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6590 2.9737 0.3905 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7392 3.0622 -0.5108 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1230 5.2094 1.0198 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8363 6.3542 1.8034 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0273 0.1870 -2.4048 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.7882 -1.1081 -2.3401 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.4500 -1.7872 -1.0158 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.2144 -2.9447 -0.8556 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1555 -0.8525 -2.4230 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5363 0.3293 -3.7028 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3373 -4.4787 -0.6428 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4882 -3.1882 0.0550 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7132 -2.2866 1.0765 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8357 -2.7920 -1.9490 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0764 0.9133 -1.9292 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4453 0.6616 2.6125 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4288 -0.3164 1.4314 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7229 0.9426 -0.4411 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6795 1.8619 0.7150 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3564 0.8587 2.0892 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3391 0.4533 3.7635 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2852 1.3363 2.5422 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5667 0.3798 3.8923 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4183 -1.4065 -0.9844 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9412 -2.4515 -2.6329 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3452 -4.1789 -2.7740 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2178 -3.6977 -1.5028 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3612 -2.3864 0.2112 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7706 -3.8703 -0.5637 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3115 -2.2727 -1.2267 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2667 2.8756 2.8958 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0737 4.9198 2.6743 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5724 3.5045 -0.1093 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7492 6.0614 2.8683 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8826 6.8188 1.4931 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6815 7.0698 1.7051 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7344 1.0110 -2.2468 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4247 -1.7819 -3.1334 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6332 -1.0695 -0.1968 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1188 -2.6584 -0.5594 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5054 -0.8296 -1.4860 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2505 0.3628 -4.3866 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 14 15 1 0 13 16 2 0 16 17 1 0 17 18 2 0 17 19 1 0 19 20 1 0 16 21 1 0 21 22 1 0 8 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 1 0 25 28 1 0 28 29 1 0 5 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 31 34 1 0 30 35 1 0 32 3 1 0 26 7 2 0 18 11 1 0 1 36 1 0 2 37 1 0 2 38 1 0 3 39 1 6 5 40 1 6 9 41 1 0 9 42 1 0 10 43 1 0 10 44 1 0 12 45 1 0 15 46 1 0 15 47 1 0 15 48 1 0 18 49 1 0 20 50 1 0 20 51 1 0 20 52 1 0 22 53 1 0 22 54 1 0 22 55 1 0 23 56 1 0 24 57 1 0 27 58 1 0 29 59 1 0 29 60 1 0 29 61 1 0 30 62 1 1 31 63 1 6 32 64 1 1 33 65 1 0 34 66 1 0 35 67 1 0 M END

Standard InCHIKey	XZLMXNUIGRSHEV-JRAQAQISSA-N
Standard InCHI	InChI=1S/C24H32O11/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/h7-10,17-18,20-21,24-29H,5-6,11H2,1-4H3/t17-,18-,20+,21-,24+/m0/s1
SMILES	OC[C@@H]1O[C@H](Oc2c(CCc3cc(OC)c(c(c3)OC)OC)ccc(c2O)OC)[C@H]([C@@H]([C@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	496.19	Volume:	478.864 ? Van der Waals volume.
Dense:	1.036	LogP:	1.343 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.643 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.43 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	18.0
TPSA:	156.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	5.0	Rings:	3.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.31	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.796	Fsp³:	0.5
MCE-18:	72.111 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.521	Fluc inhibitor:	0.086 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.138 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.561 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.123	Promiscuous compounds:	0.074

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.858	MDCK Permeability:	-5.109
Pgp-inhibitor:	0.003	Pgp-substrate:	0.053
PAMPA:	0.573 ? 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):	0.265
20% Bioavailability (F20%):	0.433	30% Bioavailability (F30%):	0.722
50% Bioavailability (F50%):	0.918

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.676	MRP1:	0.541
Plasma Protein Binding (PPB):	80.297%	Volume Distribution (VD):	-0.273
Fu:	19.328% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.995	BCRP inhibitor:	0.017
BSEP inhibitor:	0.636

ADMET: Metabolism

CYP1A2-inhibitor:	0.112	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.958	CYP2C19-substrate:	0.035
CYP2C9-inhibitor:	0.989	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.119
CYP3A4-inhibitor:	0.998	CYP3A4-substrate:	0.796
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.592 ? 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):

2.287

Half-life (T1/2):

2.523

ADMET: Toxicity

hERG Blockers:	0.088	hERG Blockers (10um):	0.437
Human Hepatotoxicity (H-HT):	0.589	Drug-induced Liver Injury (DILI):	0.537
AMES Toxicity:	0.577	Rat Oral Acute Toxicity:	0.034
Maximum Recommended Daily Dose:	0.038	Skin Sensitization:	0.972
Carcinogencity:	0.08	Eye Corrosion:	0.0
Eye Irritation:	0.088	Respiratory Toxicity:	0.074
Drug-induced Neurotoxicity:	0.039	Ototoxicity:	0.913
Hematotoxicity:	0.339	Drug-induced Nephrotoxicity:	0.818
Genotoxicity:	0.023	RPMI-8226 Immunitoxicity:	0.281
A549 Cytotoxicity:	0.542	Hek293 Cytotoxicity:	0.258
BCF:	1.297 ? 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:	3.639 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.202 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.321 ? 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
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	6
IC12	2

Activity Type	# Activity
Individual protein	2
Organism	6

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT3702	Individual protein	DNA topoisomerase 1	Saccharomyces cerevisiae S288c	IC50	=	68.7	ug.mL-1	PMID[22607678]
NPT3702	Individual protein	DNA topoisomerase 1	Saccharomyces cerevisiae S288c	IC50	>	100.0	ug.mL-1	PMID[22652224]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	IC50	=	25.0	ug.mL-1	PMID[15974617]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	IC50	>	100.0	ug.mL-1	PMID[21495717]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	IC12	>	100.0	ug ml-1	PMID[10780913]

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 NPC475096 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	18539
0.1-0.2	25803
0.2-0.3	4464
0.3-0.4	741
0.4-0.5	272
0.5-0.6	36
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	Natural Product ID
0.6716	Remote Similarity	NPC475084
0.5968	Remote Similarity	NPC69513
0.5781	Remote Similarity	NPC215833
0.5606	Remote Similarity	NPC472024
0.5606	Remote Similarity	NPC270849
0.56	Remote Similarity	NPC61594
0.5556	Remote Similarity	NPC210192
0.5556	Remote Similarity	NPC189115
0.5526	Remote Similarity	NPC56735
0.5522	Remote Similarity	NPC26653
0.5522	Remote Similarity	NPC80600
0.5441	Remote Similarity	NPC479029
0.5405	Remote Similarity	NPC148273
0.5397	Remote Similarity	NPC299144
0.5385	Remote Similarity	NPC48863
0.5385	Remote Similarity	NPC251981
0.5385	Remote Similarity	NPC13745
0.5333	Remote Similarity	NPC21902
0.5325	Remote Similarity	NPC147596
0.5323	Remote Similarity	NPC192810
0.5303	Remote Similarity	NPC9912
0.5246	Remote Similarity	NPC276195
0.5238	Remote Similarity	NPC152722
0.5224	Remote Similarity	NPC49074
0.5217	Remote Similarity	NPC105827
0.5152	Remote Similarity	NPC166040
0.5147	Remote Similarity	NPC19470
0.5139	Remote Similarity	NPC134260
0.5139	Remote Similarity	NPC469661
0.5128	Remote Similarity	NPC227902
0.5125	Remote Similarity	NPC605526
0.5072	Remote Similarity	NPC210015
0.5072	Remote Similarity	NPC210478
0.5068	Remote Similarity	NPC479030
0.5067	Remote Similarity	NPC216129
0.5067	Remote Similarity	NPC130449
0.5067	Remote Similarity	NPC248132

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC475096 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4219
0.1-0.2	4765
0.2-0.3	154
0.3-0.4	11
0.4-0.5	1
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