NPASS Compound

Structure

NPC474596 OpenBabel07101718282D 21 21 0 0 1 0 0 0 0 0999 V2000 2.5981 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5000 -0.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -2.0000 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 0.8660 1.5000 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 1.7321 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -0.5000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5981 -3.5000 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 -0.0000 1.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7321 -6.0000 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 3.4641 -3.0000 0.0000 Cl 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 -6.5000 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -6.5000 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -5.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1 10 2 0 0 0 0 2 11 2 0 0 0 0 3 16 1 0 0 0 0 4 16 1 0 0 0 0 5 7 1 0 0 0 0 5 11 1 0 0 0 0 6 8 1 0 0 0 0 6 10 1 0 0 0 0 8 14 1 0 0 0 0 9 13 1 0 0 0 0 9 21 1 0 0 0 0 10 12 1 0 0 0 0 11 13 1 0 0 0 0 12 7 1 1 0 0 0 12 16 1 0 0 0 0 13 17 1 0 0 0 0 14 16 1 0 0 0 0 14 18 1 1 0 0 0 15 19 1 0 0 0 0 15 20 1 0 0 0 0 15 21 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	369.06
Volume:	340.667
LogP:	5.91
LogD:	4.861
LogS:	-6.169
# Rotatable Bonds:	6
TPSA:	12.36
# H-Bond Aceptor:	1
# H-Bond Donor:	0
# Rings:	1
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.293
Synthetic Accessibility Score:	5.06
Fsp3:	0.688
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	2
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.745
MDCK Permeability:	1.9116328985546716e-05
Pgp-inhibitor:	0.013
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.002
20% Bioavailability (F20%):	0.007
30% Bioavailability (F30%):	0.001

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.461
Plasma Protein Binding (PPB):	92.29043579101562%
Volume Distribution (VD):	2.081
Pgp-substrate:	2.3443222045898438%

ADMET: Metabolism

CYP1A2-inhibitor:	0.247
CYP1A2-substrate:	0.627
CYP2C19-inhibitor:	0.388
CYP2C19-substrate:	0.859
CYP2C9-inhibitor:	0.415
CYP2C9-substrate:	0.8
CYP2D6-inhibitor:	0.055
CYP2D6-substrate:	0.901
CYP3A4-inhibitor:	0.339
CYP3A4-substrate:	0.516

ADMET: Excretion

Clearance (CL):	5.102
Half-life (T1/2):	0.041

ADMET: Toxicity

hERG Blockers:	0.006
Human Hepatotoxicity (H-HT):	0.212
Drug-inuced Liver Injury (DILI):	0.268
AMES Toxicity:	0.091
Rat Oral Acute Toxicity:	0.09
Maximum Recommended Daily Dose:	0.902
Skin Sensitization:	0.047
Carcinogencity:	0.379
Eye Corrosion:	0.876
Eye Irritation:	0.727
Respiratory Toxicity:	0.968

Download Data

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

Natural Product: NPC474596

Natural Product ID:	NPC474596
*Common Name:**	2-Chloro-5-((1R,3S)-3-Chloro-2,2-Dimethyl-6-Methylenecyclohexyl)-3-Methylenepentylcarbonimidic Dichloride
IUPAC Name:	1,1-dichloro-N-[2-chloro-5-[(1R,3S)-3-chloro-2,2-dimethyl-6-methylidenecyclohexyl]-3-methylidenepentyl]methanimine
Synonyms:
Standard InCHIKey:	FLQWJRAWXIZXCK-YIOYIWSBSA-N
Standard InCHI:	InChI=1S/C16H23Cl4N/c1-10-6-8-14(18)16(3,4)12(10)7-5-11(2)13(17)9-21-15(19)20/h12-14H,1-2,5-9H2,3-4H3/t12-,13?,14+/m1/s1
SMILES:	C=C(C(CN=C(Cl)Cl)Cl)CC[C@@H]1C(=C)CC[C@@H](C1(C)C)Cl
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL476493
PubChem CID:	10044705
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001550] Sesquiterpenoids

*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
NPO12253	Stylotella aurantium	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[11170682]
NPO12253	Stylotella aurantium	n.a.	n.a.	n.a.	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
IC50	4

Activity Type	# Activity
Cell Line	4

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT168	Cell Line	P388	Mus musculus	IC50	=	0.1	ug.mL-1	PMID[507638]
NPT81	Cell Line	A549	Homo sapiens	IC50	=	0.1	ug.mL-1	PMID[507638]
NPT139	Cell Line	HT-29	Homo sapiens	IC50	=	0.1	ug.mL-1	PMID[507638]
NPT170	Cell Line	SK-MEL-28	Homo sapiens	IC50	=	0.1	ug.mL-1	PMID[507638]

☑ 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 NPC474596 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	295
0.1-0.2	17406
0.2-0.3	18956
0.3-0.4	5601
0.4-0.5	359
0.5-0.6	72
0.6-0.7	6
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.8438	Intermediate Similarity	NPC475812
0.6377	Remote Similarity	NPC28755
0.6377	Remote Similarity	NPC152211
0.6301	Remote Similarity	NPC37792
0.6286	Remote Similarity	NPC311809
0.625	Remote Similarity	NPC476682
0.6197	Remote Similarity	NPC219621
0.6	Remote Similarity	NPC476681
0.5972	Remote Similarity	NPC110214
0.5914	Remote Similarity	NPC125771
0.5914	Remote Similarity	NPC218902
0.5867	Remote Similarity	NPC474456
0.5833	Remote Similarity	NPC78551
0.5833	Remote Similarity	NPC62086
0.5833	Remote Similarity	NPC227632
0.5775	Remote Similarity	NPC472830
0.5738	Remote Similarity	NPC103290
0.5735	Remote Similarity	NPC474416
0.5714	Remote Similarity	NPC318036
0.5676	Remote Similarity	NPC145715
0.5645	Remote Similarity	NPC105246
0.5645	Remote Similarity	NPC190232
0.5645	Remote Similarity	NPC193180
0.5641	Remote Similarity	NPC138409
0.5641	Remote Similarity	NPC184919
0.5634	Remote Similarity	NPC173815
0.56	Remote Similarity	NPC473959

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 NPC474596 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	180
0.1-0.2	3555
0.2-0.3	4465
0.3-0.4	897
0.4-0.5	51
0.5-0.6	2
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
0.5645	Remote Similarity	NPD1799	Clinical (unspecified phase)

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