NPASS Compound

Structure

NPC349899 OpenBabel06302215222D 21 23 0 0 1 0 0 0 0 0999 V2000 -0.8660 2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 1.5000 0.0000 O 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 -2.5981 1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5981 -0.5000 0.0000 C 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 -3.4641 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 1.0000 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -0.5000 0.0000 N 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 -2.0000 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 0.8660 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8171 -0.1910 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4049 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8171 -1.8090 0.0000 S 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 1 2 1 0 0 0 0 2 3 1 0 0 0 0 3 4 2 0 0 0 0 5 3 1 1 0 0 0 5 6 1 0 0 0 0 5 13 1 0 0 0 0 6 11 2 0 0 0 0 6 7 1 0 0 0 0 7 8 2 0 0 0 0 8 9 1 0 0 0 0 9 10 2 0 0 0 0 10 11 1 0 0 0 0 11 12 1 0 0 0 0 13 21 1 0 0 0 0 13 14 1 0 0 0 0 14 15 1 0 0 0 0 15 16 1 0 0 0 0 16 20 1 0 0 0 0 16 17 2 0 0 0 0 17 18 1 0 0 0 0 17 21 1 0 0 0 0 18 19 2 0 0 0 0 19 20 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	321.06
Volume:	306.101
LogP:	3.696
LogD:	3.489
LogS:	-3.139
# Rotatable Bonds:	4
TPSA:	29.54
# H-Bond Aceptor:	3
# H-Bond Donor:	0
# Rings:	3
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.808
Synthetic Accessibility Score:	2.779
Fsp3:	0.312
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
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:	-4.859
MDCK Permeability:	3.4177668567281216e-05
Pgp-inhibitor:	0.655
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.003
20% Bioavailability (F20%):	0.003
30% Bioavailability (F30%):	0.003

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.288
Plasma Protein Binding (PPB):	92.09276580810547%
Volume Distribution (VD):	2.449
Pgp-substrate:	7.7540507316589355%

ADMET: Metabolism

CYP1A2-inhibitor:	0.862
CYP1A2-substrate:	0.917
CYP2C19-inhibitor:	0.951
CYP2C19-substrate:	0.86
CYP2C9-inhibitor:	0.651
CYP2C9-substrate:	0.826
CYP2D6-inhibitor:	0.891
CYP2D6-substrate:	0.886
CYP3A4-inhibitor:	0.667
CYP3A4-substrate:	0.912

ADMET: Excretion

Clearance (CL):	9.604
Half-life (T1/2):	0.118

ADMET: Toxicity

hERG Blockers:	0.158
Human Hepatotoxicity (H-HT):	0.913
Drug-inuced Liver Injury (DILI):	0.556
AMES Toxicity:	0.015
Rat Oral Acute Toxicity:	0.243
Maximum Recommended Daily Dose:	0.519
Skin Sensitization:	0.048
Carcinogencity:	0.085
Eye Corrosion:	0.003
Eye Irritation:	0.012
Respiratory Toxicity:	0.619

Download Data

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

Natural Product: NPC349899

Natural Product ID:	NPC349899
*Common Name:**	GKTWGGQPFAXNFI-HNNXBMFYSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	GKTWGGQPFAXNFI-HNNXBMFYSA-N
Standard InCHI:	InChI=1S/C16H16ClNO2S/c1-20-16(19)15(12-4-2-3-5-13(12)17)18-8-6-14-11(10-18)7-9-21-14/h2-5,7,9,15H,6,8,10H2,1H3/t15-/m0/s1
SMILES:	COC(=O)[C@H](c1ccccc1Cl)N1CCc2c(ccs2)C1
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	60606
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:0000394] Alpha amino acid esters

*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
NPO11796	Morus australis	Species	Moraceae	Eukaryota	n.a.	root	n.a.	PMID[17405024]
NPO11796	Morus australis	Species	Moraceae	Eukaryota	Root Bark	n.a.	n.a.	PMID[27908762]
NPO11796	Morus australis	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9358644]
NPO11796	Morus australis	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11796	Morus australis	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11796	Morus australis	Species	Moraceae	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
ED50	2
IC50	4
Ki	4
Others	45

Activity Type	# Activity
Individual Protein	11
NON-MOLECULAR	9
Organism	31
Others	3
SINGLE PROTEIN	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT627	Individual Protein	Cytochrome P450 2B6	Homo sapiens	Ki	=	500.0	nM	PMID[16248836]
NPT627	Individual Protein	Cytochrome P450 2B6	Homo sapiens	Ki	=	1100.0	nM	PMID[16248836]
NPT627	Individual Protein	Cytochrome P450 2B6	Homo sapiens	Ki	=	500.0	nM	PMID[22409598]
NPT213	Individual Protein	Cytochrome P450 2C19	Homo sapiens	Ki	=	14300.0	nM	PMID[22409598]
NPT627	Individual Protein	Cytochrome P450 2B6	Homo sapiens	Inhibition	=	44.0	%	PMID[21467212]
NPT208	Individual Protein	Cytochrome P450 1A2	Homo sapiens	Inhibition	<	10.0	%	PMID[21467212]
NPT628	Individual Protein	Cytochrome P450 2C8	Homo sapiens	Inhibition	<	10.0	%	PMID[21467212]
NPT212	Individual Protein	Cytochrome P450 2C9	Homo sapiens	Inhibition	<	10.0	%	PMID[21467212]
NPT213	Individual Protein	Cytochrome P450 2C19	Homo sapiens	Inhibition	=	10.0	%	PMID[21467212]
NPT110	Individual Protein	Cytochrome P450 2D6	Homo sapiens	Inhibition	<	10.0	%	PMID[21467212]
NPT109	Individual Protein	Cytochrome P450 3A4	Homo sapiens	Inhibition	=	35.0	%	PMID[21467212]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	Inhibition	=	85.2	%	PMID[22055718]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	Inhibition	=	3.5	%	PMID[22055718]
NPT605	Organism	Homo sapiens	Homo sapiens	Activity	=	52.0	%	PMID[22409598]
NPT605	Organism	Homo sapiens	Homo sapiens	Activity	=	60.0	%	PMID[22409598]
NPT1016	Organism	Canis familiaris	Canis lupus familiaris	ED50	=	15.0	mg.kg-1	PMID[23899349]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	Inhibition	=	80.2	%	PMID[24387347]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Activity	=	67.0	%	PMID[24164581]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	FC	=	8.2	n.a.	PMID[24164581]
NPT2	Others	Unspecified		IC50	=	150000.0	nM	PMID[24393581]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	60.0	%	PMID[24859764]
NPT32	Organism	Mus musculus	Mus musculus	FC	=	2.3	n.a.	PMID[24859764]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	FC	=	8.2	n.a.	PMID[24513044]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	FC	=	6.2	n.a.	PMID[24513044]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Activity	=	67.0	%	PMID[24513044]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	ED50	=	2.6	mg.kg-1	PMID[25075638]
NPT419	Organism	Oryctolagus cuniculus	Oryctolagus cuniculus	FC	=	6.0	n.a.	PMID[24931384]
NPT27	Others	Unspecified		IC50	=	50.0	nM	PMID[22232427]
NPT27	Others	Unspecified		IC50	=	140.0	nM	PMID[22232427]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	Inhibition	=	94.5	%	DOI[10.1039/C4MD00022F]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	Inhibition	=	92.3	%	DOI[10.1039/C4MD00022F]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	Inhibition	=	77.6	%	DOI[10.1039/C4MD00022F]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	Inhibition	=	86.9	%	DOI[10.1039/C4MD00022F]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	7600.0	nM	DOI[10.1039/C4MD00022F]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	70.0	%	PMID[26807542]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	50.0	%	PMID[26807542]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	Activity	=	93.3	%	PMID[27908762]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Activity	=	0.077	g	PMID[31563807]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Activity	=	0.253	g	PMID[31563807]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Activity	=	46.1	%	PMID[31563807]
NPT20556	SINGLE PROTEIN	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	17.95	%	DOI[10.6019/CHEMBL4495564]
NPT20555	ORGANISM	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	0.03	%	DOI[10.6019/CHEMBL4495565]
NPT20	Organism	Candida albicans	Candida albicans	Inhibition	=	2.18	%	DOI[10.6019/CHEMBL4296181]
NPT85	Organism	Filobasidiella neoformans	Cryptococcus neoformans	Inhibition	=	-8.15	%	DOI[10.6019/CHEMBL4296181]
NPT19	Organism	Escherichia coli	Escherichia coli	Inhibition	=	-0.51	%	DOI[10.6019/CHEMBL4296181]
NPT173	Organism	Klebsiella pneumoniae	Klebsiella pneumoniae	Inhibition	=	14.99	%	DOI[10.6019/CHEMBL4296181]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	Inhibition	=	15.58	%	DOI[10.6019/CHEMBL4296181]
NPT747	Organism	Acinetobacter baumannii	Acinetobacter baumannii	Inhibition	=	23.6	%	DOI[10.6019/CHEMBL4296181]
NPT2922	Organism	Staphylococcus aureus subsp. aureus	Staphylococcus aureus subsp. aureus	Inhibition	=	12.7	%	DOI[10.6019/CHEMBL4296181]
NPT4697	Organism	Cynomolgus monkey	Macaca fascicularis	FC	=	7.3	n.a.	PMID[33049608]
NPT4697	Organism	Cynomolgus monkey	Macaca fascicularis	FC	>	10.0	n.a.	PMID[33049608]
NPT4697	Organism	Cynomolgus monkey	Macaca fascicularis	Activity	=	48.0	%	PMID[33049608]
NPT4697	Organism	Cynomolgus monkey	Macaca fascicularis	FC	=	8.1	n.a.	PMID[33049608]

☑ 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 NPC349899 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	208
0.1-0.2	2200
0.2-0.3	12782
0.3-0.4	18914
0.4-0.5	7729
0.5-0.6	835
0.6-0.7	27
0.7-0.8	1
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

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 NPC349899 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	139
0.1-0.2	675
0.2-0.3	1019
0.3-0.4	2467
0.4-0.5	3539
0.5-0.6	1185
0.6-0.7	119
0.7-0.8	5
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	2

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