NPASS Compound

Structure

NPC474129 OpenBabel07101718182D 25 29 0 0 1 0 0 0 0 0999 V2000 1.0890 -1.9960 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5697 -3.1392 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9865 -3.7189 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5874 -2.2791 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1044 -2.7897 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8769 -1.0190 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7252 -0.4679 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6195 -1.4200 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0321 -0.8592 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.2787 -1.7791 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1826 -1.1958 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9348 -2.5671 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4643 -1.2601 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7809 -1.9560 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9217 -1.9881 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0000 -1.0000 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 1.8660 -0.5000 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 1.0000 0.0000 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 -2.2780 -1.7417 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1819 -1.1584 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3129 -2.8027 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5871 -3.3251 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4544 -2.8722 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 18 1 0 0 0 0 2 24 1 0 0 0 0 3 25 1 0 0 0 0 4 5 1 0 0 0 0 4 9 2 0 0 0 0 5 14 2 0 0 0 0 6 10 2 0 0 0 0 6 12 1 0 0 0 0 7 11 1 0 0 0 0 7 18 1 0 0 0 0 8 13 2 0 0 0 0 8 19 1 0 0 0 0 9 10 1 0 0 0 0 9 15 1 0 0 0 0 10 11 1 0 0 0 0 11 20 1 6 0 0 0 12 14 1 0 0 0 0 12 21 2 0 0 0 0 13 16 1 0 0 0 0 13 22 1 0 0 0 0 14 24 1 0 0 0 0 15 17 2 0 0 0 0 15 19 1 0 0 0 0 16 17 1 0 0 0 0 16 23 2 0 0 0 0 17 25 1 0 0 0 0 18 19 1 0 0 0 0 18 20 1 0 0 0 0 19 20 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	339.11
Volume:	330.891
LogP:	0.894
LogD:	1.281
LogS:	-4.422
# Rotatable Bonds:	2
TPSA:	72.68
# H-Bond Aceptor:	6
# H-Bond Donor:	0
# Rings:	5
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.596
Synthetic Accessibility Score:	5.083
Fsp3:	0.421
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	1

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.85
MDCK Permeability:	2.7644722649711184e-05
Pgp-inhibitor:	0.911
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.01
20% Bioavailability (F20%):	0.968
30% Bioavailability (F30%):	0.968

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.455
Plasma Protein Binding (PPB):	75.93285369873047%
Volume Distribution (VD):	1.203
Pgp-substrate:	10.488243103027344%

ADMET: Metabolism

CYP1A2-inhibitor:	0.053
CYP1A2-substrate:	0.739
CYP2C19-inhibitor:	0.716
CYP2C19-substrate:	0.909
CYP2C9-inhibitor:	0.943
CYP2C9-substrate:	0.421
CYP2D6-inhibitor:	0.21
CYP2D6-substrate:	0.083
CYP3A4-inhibitor:	0.945
CYP3A4-substrate:	0.967

ADMET: Excretion

Clearance (CL):	4.024
Half-life (T1/2):	0.276

ADMET: Toxicity

hERG Blockers:	0.001
Human Hepatotoxicity (H-HT):	0.336
Drug-inuced Liver Injury (DILI):	0.912
AMES Toxicity:	0.133
Rat Oral Acute Toxicity:	0.074
Maximum Recommended Daily Dose:	0.792
Skin Sensitization:	0.159
Carcinogencity:	0.224
Eye Corrosion:	0.003
Eye Irritation:	0.017
Respiratory Toxicity:	0.27

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC474129

Natural Product ID:	NPC474129
*Common Name:**	Demecolcinone
IUPAC Name:	n.a.
Synonyms:	Demecolcinone
Standard InCHIKey:	JHQXILBWKAUJFN-VGENCSJCSA-N
Standard InCHI:	InChI=1S/C19H17NO5/c1-18-7-11-10-6-12(21)14(24-2)5-4-9(10)15-17(25-3)16(23)13(22)8-19(15,18)20(11)18/h4-6,8,11,22H,7H2,1-3H3/t11-,18?,19?,20?/m1/s1
SMILES:	CC12CC3N1C24C=C(C(=O)C(=C4C5=CC=C(C(=O)C=C35)OC)OC)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL462714
PubChem CID:	44583926
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004150] Hydrocarbon derivatives [CHEMONTID:0001650] Tropones

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO24146	Colchicum brachyphyllum	Species	Colchicaceae	Eukaryota	n.a.	Jordanian	n.a.	PMID[15730238]
NPO24146	Colchicum brachyphyllum	Species	Colchicaceae	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	NP ID	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
EC50	3
MIC	4
Others	1

Activity Type	# Activity
Cell Line	3
Organism	5

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT83	Cell Line	MCF7	Homo sapiens	EC50	=	28700.0	nM	PMID[470901]
NPT397	Cell Line	NCI-H460	Homo sapiens	EC50	=	31300.0	nM	PMID[470901]
NPT395	Cell Line	SF-268	Homo sapiens	EC50	=	28400.0	nM	PMID[470901]
NPT140	Organism	Artemia	Artemia	LC50	=	79.3	ug.mL-1	PMID[470901]
NPT729	Organism	Micrococcus luteus	Micrococcus luteus	MIC	>	500.0	ug.mL-1	PMID[470901]
NPT602	Organism	Mycobacterium smegmatis	Mycobacterium smegmatis	MIC	>	500.0	ug.mL-1	PMID[470901]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	MIC	>	500.0	ug.mL-1	PMID[470901]
NPT21	Organism	Aspergillus niger	Aspergillus niger	MIC	>	500.0	ug.mL-1	PMID[470901]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC474129 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	236
0.1-0.2	1614
0.2-0.3	6302
0.3-0.4	10891
0.4-0.5	6853
0.5-0.6	15263
0.6-0.7	1515
0.7-0.8	22
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.6061	Remote Similarity	NPC26504
0.6034	Remote Similarity	NPC476328
0.602	Remote Similarity	NPC147438
0.6	Remote Similarity	NPC76283
0.5932	Remote Similarity	NPC476276
0.5922	Remote Similarity	NPC99308
0.5849	Remote Similarity	NPC470177
0.5826	Remote Similarity	NPC34193
0.5812	Remote Similarity	NPC133420
0.5776	Remote Similarity	NPC473289
0.5763	Remote Similarity	NPC185929
0.576	Remote Similarity	NPC471673
0.5714	Remote Similarity	NPC176773
0.5676	Remote Similarity	NPC299808
0.5676	Remote Similarity	NPC72183
0.5676	Remote Similarity	NPC110875
0.5676	Remote Similarity	NPC118844
0.5673	Remote Similarity	NPC476560
0.5669	Remote Similarity	NPC13351
0.5667	Remote Similarity	NPC24596
0.5657	Remote Similarity	NPC474539
0.5644	Remote Similarity	NPC34672
0.562	Remote Similarity	NPC274895
0.5619	Remote Similarity	NPC312419
0.5612	Remote Similarity	NPC474060
0.5603	Remote Similarity	NPC316730

Chemically structural similarity: II. Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC474129 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	168
0.1-0.2	698
0.2-0.3	1046
0.3-0.4	1883
0.4-0.5	2730
0.5-0.6	2211
0.6-0.7	403
0.7-0.8	11
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

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