NPASS Compound

Structure

CID201713 OpenBabel06191715592D 31 30 0 0 1 0 0 0 0 0999 V2000 7.2579 -1.4303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0036 -0.4813 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8958 -2.6324 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4638 -2.6670 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4813 -1.6846 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4638 -0.7021 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8130 -0.9051 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9374 -2.5354 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0126 -1.0829 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2328 -1.9048 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4462 -1.6846 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9198 -2.5354 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6653 -0.7356 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1057 -2.3792 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6142 -0.4813 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 6.3089 -1.1760 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0547 -2.1250 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 1.4638 -1.6846 0.0000 N 0 3 0 0 0 0 0 0 0 0 0 0 4.4110 -1.6846 0.0000 N 0 3 3 0 0 0 0 0 0 0 0 0 2.8880 -5.4260 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4440 -3.6297 0.0000 O 0 5 0 0 0 0 0 0 0 0 0 0 0.4813 -4.5923 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4440 -5.5550 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4067 -4.5923 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4440 -4.5923 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 10.6272 -2.2777 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1832 -0.4813 0.0000 O 0 5 0 0 0 0 0 0 0 0 0 0 8.2205 -1.4440 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 9.1832 -2.4067 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 10.1459 -1.4440 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 9.1832 -1.4440 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 1 16 1 0 0 0 0 2 16 1 0 0 0 0 3 17 1 0 0 0 0 4 18 1 0 0 0 0 5 18 1 0 0 0 0 6 18 1 0 0 0 0 7 19 1 0 0 0 0 8 11 1 0 0 0 0 8 12 1 0 0 0 0 9 10 1 0 0 0 0 9 15 1 0 0 0 0 10 17 1 0 0 0 0 11 18 1 0 0 0 0 12 19 1 0 0 0 0 13 15 1 0 0 0 0 13 19 1 0 0 0 0 14 17 1 0 0 0 0 14 19 1 0 0 0 0 15 16 1 0 0 0 0 16 17 1 0 0 0 0 20 24 1 0 0 0 0 21 25 1 0 0 0 0 22 25 2 0 0 0 0 23 25 2 0 0 0 0 24 25 1 0 0 0 0 26 30 1 0 0 0 0 27 31 1 0 0 0 0 28 31 2 0 0 0 0 29 31 2 0 0 0 0 30 31 1 0 0 0 0 M CHG 4 18 1 19 1 21 -1 27 -1 M END $$$$

Physi-Chem Properties

Molecular Weight:	268.29
Volume:	310.105
LogP:	-1.387
LogD:	-0.531
LogS:	0.321
# Rotatable Bonds:	4
TPSA:	0.0
# H-Bond Aceptor:	2
# H-Bond Donor:	0
# Rings:	2
# Heavy Atoms:	2

MedChem Properties

QED Drug-Likeness Score:	0.688
Synthetic Accessibility Score:	5.338
Fsp3:	1.0
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.661
MDCK Permeability:	6.326418770186137e-06
Pgp-inhibitor:	0.0
Pgp-substrate:	0.996
Human Intestinal Absorption (HIA):	0.976
20% Bioavailability (F20%):	1.0
30% Bioavailability (F30%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.022
Plasma Protein Binding (PPB):	25.52294158935547%
Volume Distribution (VD):	0.521
Pgp-substrate:	75.30425262451172%

ADMET: Metabolism

CYP1A2-inhibitor:	0.001
CYP1A2-substrate:	0.303
CYP2C19-inhibitor:	0.005
CYP2C19-substrate:	0.072
CYP2C9-inhibitor:	0.0
CYP2C9-substrate:	0.098
CYP2D6-inhibitor:	0.001
CYP2D6-substrate:	0.926
CYP3A4-inhibitor:	0.001
CYP3A4-substrate:	0.105

ADMET: Excretion

Clearance (CL):	5.498
Half-life (T1/2):	0.962

ADMET: Toxicity

hERG Blockers:	0.006
Human Hepatotoxicity (H-HT):	0.015
Drug-inuced Liver Injury (DILI):	0.001
AMES Toxicity:	0.002
Rat Oral Acute Toxicity:	0.126
Maximum Recommended Daily Dose:	0.942
Skin Sensitization:	0.188
Carcinogencity:	0.047
Eye Corrosion:	0.382
Eye Irritation:	0.103
Respiratory Toxicity:	0.982

Download Data

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

Natural Product: NPC201713

Natural Product ID:	NPC201713
*Common Name:**	Trimethidinium Methosulfate
IUPAC Name:	methyl sulfate;trimethyl-[3-(3,5,8,8-tetramethyl-3-azoniabicyclo[3.2.1]octan-3-yl)propyl]azanium
Synonyms:	Methocamphone Methylsulfate; Trimethidinium Methosulfate; Trimethidinium Methosulphate
Standard InCHIKey:	ZOSQTCOGKFRDET-UHFFFAOYSA-L
Standard InCHI:	InChI=1S/C17H36N2.2CH4O4S/c1-16(2)15-9-10-17(16,3)14-19(7,13-15)12-8-11-18(4,5)6;21-5-6(2,3)4/h15H,8-14H2,1-7H3;21H3,(H,2,3,4)/q+2;;/p-2
SMILES:	C[N+](CCC[N+]1(C)CC2CCC(C1)(C2(C)C)C)(C)C.COS(=O)(=O)[O-].COS(=O)(=O)[O-]
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL2107688
PubChem CID:	26483
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000307] Azepanes

*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
NPO16755	Saposhnikovia divaricata	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17703773]
NPO16755	Saposhnikovia divaricata	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO16755	Saposhnikovia divaricata	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16755	Saposhnikovia divaricata	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]

☑ 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
Potency	2

Activity Type	# Activity
Individual Protein	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT50	Individual Protein	Tyrosyl-DNA phosphodiesterase 1	Homo sapiens	Potency	n.a.	9441.1	nM	PMID[534599]
NPT50	Individual Protein	Tyrosyl-DNA phosphodiesterase 1	Homo sapiens	Potency	n.a.	33498.3	nM	PMID[534599]

☑ 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 NPC201713 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	188
0.1-0.2	19411
0.2-0.3	16791
0.3-0.4	5810
0.4-0.5	455
0.5-0.6	40
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	1

Similarity Score	Similarity Level	Natural Product ID
0.7119	Intermediate Similarity	NPC21781
0.6667	Remote Similarity	NPC53276
0.6562	Remote Similarity	NPC469970
0.6379	Remote Similarity	NPC472828
0.6324	Remote Similarity	NPC473442
0.6324	Remote Similarity	NPC120167
0.6269	Remote Similarity	NPC271640
0.6207	Remote Similarity	NPC243635
0.6207	Remote Similarity	NPC151004
0.6207	Remote Similarity	NPC228980
0.6176	Remote Similarity	NPC245223
0.6176	Remote Similarity	NPC124384
0.6154	Remote Similarity	NPC15231
0.6129	Remote Similarity	NPC231129
0.6078	Remote Similarity	NPC471575
0.6078	Remote Similarity	NPC471440
0.6032	Remote Similarity	NPC82919
0.6	Remote Similarity	NPC21773
0.5965	Remote Similarity	NPC153803
0.589	Remote Similarity	NPC7214
0.589	Remote Similarity	NPC25110
0.5833	Remote Similarity	NPC476904
0.5833	Remote Similarity	NPC475272
0.5789	Remote Similarity	NPC12035
0.5775	Remote Similarity	NPC265789
0.5769	Remote Similarity	NPC171639
0.5769	Remote Similarity	NPC153734
0.5753	Remote Similarity	NPC125828
0.5714	Remote Similarity	NPC181141
0.5672	Remote Similarity	NPC476559
0.5625	Remote Similarity	NPC472830

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 NPC201713 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	80
0.1-0.2	3851
0.2-0.3	4171
0.3-0.4	907
0.4-0.5	120
0.5-0.6	16
0.6-0.7	3
0.7-0.8	2
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
0.8113	Intermediate Similarity	NPD3712	Phase 3
0.8113	Intermediate Similarity	NPD3711	Phase 3
0.8039	Intermediate Similarity	NPD4834	Discontinued
0.7885	Intermediate Similarity	NPD5793	Discontinued
0.7778	Intermediate Similarity	NPD3727	Discontinued
0.7647	Intermediate Similarity	NPD5379	Clinical (unspecified phase)
0.7347	Intermediate Similarity	NPD2701	Discontinued
0.6667	Remote Similarity	NPD4839	Approved
0.6207	Remote Similarity	NPD1822	Approved
0.6207	Remote Similarity	NPD1821	Approved
0.6207	Remote Similarity	NPD3722	Approved
0.6207	Remote Similarity	NPD1823	Approved
0.6207	Remote Similarity	NPD3721	Approved
0.5957	Remote Similarity	NPD5385	Approved
0.5957	Remote Similarity	NPD5384	Approved
0.5957	Remote Similarity	NPD2274	Approved
0.5957	Remote Similarity	NPD2275	Approved
0.5867	Remote Similarity	NPD7155	Clinical (unspecified phase)
0.5806	Remote Similarity	NPD628	Phase 3
0.5806	Remote Similarity	NPD627	Approved
0.5806	Remote Similarity	NPD625	Approved
0.5806	Remote Similarity	NPD626	Phase 3
0.5745	Remote Similarity	NPD3734	Approved
0.5745	Remote Similarity	NPD2706	Approved
0.5745	Remote Similarity	NPD2705	Approved

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