NPASS Compound

Structure

NPC14741 OpenBabel06302215272D 22 22 0 0 1 0 0 0 0 0999 V2000 -5.1962 -6.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 -6.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -6.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -6.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -5.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -4.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -3.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -2.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 1.5000 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 0.0000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 1.5000 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 2.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -2.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -3.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 3 1 0 0 0 0 3 4 2 0 0 0 0 3 5 1 0 0 0 0 5 6 2 0 0 0 0 6 7 1 0 0 0 0 7 8 2 3 0 0 0 7 22 1 0 0 0 0 8 9 1 0 0 0 0 9 10 1 1 0 0 0 9 19 1 0 0 0 0 10 11 1 0 0 0 0 11 16 2 0 0 0 0 11 12 1 0 0 0 0 12 13 2 0 0 0 0 13 14 1 0 0 0 0 14 15 2 0 0 0 0 14 18 1 0 0 0 0 15 16 1 0 0 0 0 15 17 1 0 0 0 0 19 20 2 0 0 0 0 19 21 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	327.05
Volume:	302.638
LogP:	0.904
LogD:	0.636
LogS:	-1.388
# Rotatable Bonds:	8
TPSA:	113.26
# H-Bond Aceptor:	7
# H-Bond Donor:	2
# Rings:	1
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.606
Synthetic Accessibility Score:	2.668
Fsp3:	0.286
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.453
MDCK Permeability:	1.790864553186111e-05
Pgp-inhibitor:	0.003
Pgp-substrate:	0.002
Human Intestinal Absorption (HIA):	0.174
20% Bioavailability (F20%):	0.014
30% Bioavailability (F30%):	0.354

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.123
Plasma Protein Binding (PPB):	73.37692260742188%
Volume Distribution (VD):	0.28
Pgp-substrate:	27.98943519592285%

ADMET: Metabolism

CYP1A2-inhibitor:	0.08
CYP1A2-substrate:	0.107
CYP2C19-inhibitor:	0.125
CYP2C19-substrate:	0.052
CYP2C9-inhibitor:	0.111
CYP2C9-substrate:	0.496
CYP2D6-inhibitor:	0.021
CYP2D6-substrate:	0.186
CYP3A4-inhibitor:	0.025
CYP3A4-substrate:	0.218

ADMET: Excretion

Clearance (CL):	4.85
Half-life (T1/2):	0.943

ADMET: Toxicity

hERG Blockers:	0.009
Human Hepatotoxicity (H-HT):	0.344
Drug-inuced Liver Injury (DILI):	0.945
AMES Toxicity:	0.013
Rat Oral Acute Toxicity:	0.029
Maximum Recommended Daily Dose:	0.009
Skin Sensitization:	0.189
Carcinogencity:	0.075
Eye Corrosion:	0.003
Eye Irritation:	0.015
Respiratory Toxicity:	0.027

Download Data

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

Natural Product: NPC14741

Natural Product ID:	NPC14741
*Common Name:**	KCOKHEIACSQLBQ-ORAHPGNNSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	KCOKHEIACSQLBQ-ORAHPGNNSA-N
Standard InCHI:	InChI=1S/C14H14ClNO6/c1-22-13(19)5-4-12(18)16-10(14(20)21)7-8-2-3-11(17)9(15)6-8/h2-6,10,17H,7H2,1H3,(H,16,18)(H,20,21)/b5-4+/t10-/m1/s1
SMILES:	COC(=O)/C=C/C(=N[C@H](Cc1ccc(c(c1)Cl)O)C(=O)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	11290362
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000347] Amino acids and derivatives [CHEMONTID:0000060] Alpha amino acids and derivatives [CHEMONTID:0004319] Tyrosine and derivatives

*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
NPO33440	Xylaria sp.	Species	Xylariaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15921427]
NPO33440	Xylaria sp.	Species	Xylariaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17892262]
NPO33440	Xylaria sp.	Species	Xylariaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18500842]
NPO33440	Xylaria sp.	Species	Xylariaceae	Eukaryota	Isolated from the lichen Leptogium saturninum (Dicks.) Nyl.	Zixi Mountain, Yunnan, China	2006-NOV	PMID[21428374]

☑ 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
Ki	6
Others	10

Activity Type	# Activity
Individual Protein	6
Organism	2
Others	8

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT3155	Individual Protein	PROBABLE TRANSMEMBRANE CARBONIC ANHYDRASE (CARBONATE DEHYDRATASE) (CARBONIC DEHYDRATASE)	Mycobacterium tuberculosis	Ki	=	11300.0	nM	PMID[21332115]
NPT3156	Individual Protein	Uncharacterized protein Rv1284/MT1322	Mycobacterium tuberculosis	Ki	=	840.0	nM	PMID[21332115]
NPT1148	Individual Protein	Carbonic anhydrase	Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast)	Ki	=	1030.0	nM	PMID[21332115]
NPT3157	Individual Protein	Carbonic anhydrase 2	Cryptococcus neoformans var. grubii	Ki	=	1150.0	nM	PMID[21332115]
NPT233	Individual Protein	Carbonic anhydrase II	Homo sapiens	Ki	=	8300.0	nM	PMID[21332115]
NPT176	Organism	Artemia salina	Artemia salina	Activity	=	0.0	%	PMID[15921427]
NPT176	Organism	Artemia salina	Artemia salina	Activity	=	71.0	%	PMID[15921427]
NPT947	Individual Protein	Carbonic anhydrase I	Homo sapiens	Ki	=	239000.0	nM	PMID[21332115]
NPT2	Others	Unspecified		Ratio Ki	=	21.2	n.a.	PMID[21332115]
NPT2	Others	Unspecified		Ratio Ki	=	284.5	n.a.	PMID[21332115]
NPT2	Others	Unspecified		Ratio Ki	=	232.0	n.a.	PMID[21332115]
NPT2	Others	Unspecified		Ratio Ki	=	207.8	n.a.	PMID[21332115]
NPT2	Others	Unspecified		Ratio Ki	=	0.7	n.a.	PMID[21332115]
NPT2	Others	Unspecified		Ratio Ki	=	9.9	n.a.	PMID[21332115]
NPT2	Others	Unspecified		Ratio Ki	=	8.1	n.a.	PMID[21332115]
NPT2	Others	Unspecified		Ratio Ki	=	7.2	n.a.	PMID[21332115]

☑ 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 NPC14741 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	180
0.1-0.2	1506
0.2-0.3	5659
0.3-0.4	11717
0.4-0.5	9649
0.5-0.6	12489
0.6-0.7	1413
0.7-0.8	74
0.8-0.85	8
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID

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 NPC14741 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	131
0.1-0.2	611
0.2-0.3	1062
0.3-0.4	2088
0.4-0.5	2814
0.5-0.6	2088
0.6-0.7	332
0.7-0.8	24
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

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