NPASS Compound

Structure

CID327257 OpenBabel06191716192D 22 22 0 0 1 0 0 0 0 0999 V2000 2.2195 3.2154 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4535 1.2877 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2195 3.2154 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4535 1.2877 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5741 2.2804 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 1.4709 3.8786 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 1.8855 0.4647 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 -0.4709 3.8786 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 -0.8855 0.4647 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 0.5000 4.1179 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 1.0000 -0.0000 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 3.5668 2.4010 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9357 4.7640 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5486 -0.2838 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9357 4.7640 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5486 -0.2838 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 5.1179 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2393 -0.9709 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2393 -0.9709 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5668 2.4010 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5741 2.2804 0.0000 S 0 0 3 0 0 0 0 0 0 0 0 0 1 5 1 0 0 0 0 1 6 1 0 0 0 0 2 5 1 0 0 0 0 2 7 1 0 0 0 0 3 8 1 0 0 0 0 3 22 1 0 0 0 0 4 9 1 0 0 0 0 4 22 1 0 0 0 0 5 13 1 0 0 0 0 6 10 1 0 0 0 0 6 14 1 0 0 0 0 7 11 1 0 0 0 0 7 15 1 0 0 0 0 8 10 1 0 0 0 0 8 16 1 0 0 0 0 9 12 1 0 0 0 0 9 17 1 0 0 0 0 10 18 1 0 0 0 0 11 12 1 0 0 0 0 11 19 1 0 0 0 0 12 20 1 0 0 0 0 21 22 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	344.11
Volume:	305.173
LogP:	-3.26
LogD:	-3.032
LogS:	0.144
# Rotatable Bonds:	0
TPSA:	184.9
# H-Bond Aceptor:	9
# H-Bond Donor:	8
# Rings:	1
# Heavy Atoms:	10

MedChem Properties

QED Drug-Likeness Score:	0.2
Synthetic Accessibility Score:	5.607
Fsp3:	1.0
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	1
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.469
MDCK Permeability:	0.00022815506963524967
Pgp-inhibitor:	0.003
Pgp-substrate:	0.977
Human Intestinal Absorption (HIA):	0.943
20% Bioavailability (F20%):	0.958
30% Bioavailability (F30%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.423
Plasma Protein Binding (PPB):	12.166815757751465%
Volume Distribution (VD):	0.96
Pgp-substrate:	61.905513763427734%

ADMET: Metabolism

CYP1A2-inhibitor:	0.002
CYP1A2-substrate:	0.016
CYP2C19-inhibitor:	0.004
CYP2C19-substrate:	0.058
CYP2C9-inhibitor:	0.0
CYP2C9-substrate:	0.608
CYP2D6-inhibitor:	0.0
CYP2D6-substrate:	0.095
CYP3A4-inhibitor:	0.001
CYP3A4-substrate:	0.001

ADMET: Excretion

Clearance (CL):	1.174
Half-life (T1/2):	0.742

ADMET: Toxicity

hERG Blockers:	0.091
Human Hepatotoxicity (H-HT):	0.185
Drug-inuced Liver Injury (DILI):	0.013
AMES Toxicity:	0.039
Rat Oral Acute Toxicity:	0.025
Maximum Recommended Daily Dose:	0.806
Skin Sensitization:	0.02
Carcinogencity:	0.024
Eye Corrosion:	0.003
Eye Irritation:	0.015
Respiratory Toxicity:	0.163

Download Data

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

Natural Product: NPC327257

Natural Product ID:	NPC327257
*Common Name:**	1-Oxo-1$L^{4}-Thiacyclotridecane-3,4,5,6,8,10,11,12-Octol
IUPAC Name:	1-oxo-1$l^{4}-thiacyclotridecane-3,4,5,6,8,10,11,12-octol
Synonyms:
Standard InCHIKey:	ZCFDZGVJJBUOOF-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C12H24O9S/c13-5-1-6(14)10(18)8(16)3-22(21)4-9(17)12(20)11(19)7(15)2-5/h5-20H,1-4H2
SMILES:	OC1CC(O)C(O)C(O)CS(=O)CC(C(C(C(C1)O)O)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL460255
PubChem CID:	24808560
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000004] Organosulfur compounds [CHEMONTID:0000491] Sulfoxides

*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
NPO20734	Salacia reticulata	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1248/yakushi.121.371]
NPO20734	Salacia reticulata	Species	Celastraceae	Eukaryota	n.a.	stem	n.a.	PMID[18547114]
NPO20734	Salacia reticulata	Species	Celastraceae	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
IC50	3
Ki	3

Activity Type	# Activity
Individual Protein	6

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT462	Individual Protein	Sucrase-isomaltase	Rattus norvegicus	IC50	=	186.0	nM	PMID[464839]
NPT462	Individual Protein	Sucrase-isomaltase	Rattus norvegicus	IC50	=	99.0	nM	PMID[464839]
NPT462	Individual Protein	Sucrase-isomaltase	Rattus norvegicus	Ki	=	52.0	nM	PMID[464839]
NPT462	Individual Protein	Sucrase-isomaltase	Rattus norvegicus	Ki	=	4200.0	nM	PMID[464839]
NPT671	Individual Protein	Acidic alpha-glucosidase	Rattus norvegicus	IC50	=	227.0	nM	PMID[464839]
NPT671	Individual Protein	Acidic alpha-glucosidase	Rattus norvegicus	Ki	=	110.0	nM	PMID[464839]

☑ 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 NPC327257 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	1562
0.1-0.2	16764
0.2-0.3	18472
0.3-0.4	5268
0.4-0.5	522
0.5-0.6	100
0.6-0.7	8
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
0.64	Remote Similarity	NPC325034
0.64	Remote Similarity	NPC86412
0.64	Remote Similarity	NPC192065
0.64	Remote Similarity	NPC293908
0.64	Remote Similarity	NPC66052
0.6197	Remote Similarity	NPC320012
0.5965	Remote Similarity	NPC62014
0.5818	Remote Similarity	NPC99573
0.5818	Remote Similarity	NPC266553
0.5818	Remote Similarity	NPC111882
0.5818	Remote Similarity	NPC88278
0.5818	Remote Similarity	NPC102981
0.5818	Remote Similarity	NPC227707
0.58	Remote Similarity	NPC182541
0.58	Remote Similarity	NPC149070
0.58	Remote Similarity	NPC187058
0.58	Remote Similarity	NPC267243
0.58	Remote Similarity	NPC197207
0.58	Remote Similarity	NPC127074
0.5763	Remote Similarity	NPC314613
0.5692	Remote Similarity	NPC148424
0.5686	Remote Similarity	NPC319034
0.5686	Remote Similarity	NPC193062
0.5686	Remote Similarity	NPC1748
0.5686	Remote Similarity	NPC72324
0.5686	Remote Similarity	NPC66124
0.5672	Remote Similarity	NPC174485
0.566	Remote Similarity	NPC474914
0.566	Remote Similarity	NPC474392
0.5645	Remote Similarity	NPC326533

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 NPC327257 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	1712
0.1-0.2	5389
0.2-0.3	1551
0.3-0.4	367
0.4-0.5	93
0.5-0.6	34
0.6-0.7	4
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
0.7273	Intermediate Similarity	NPD9669	Clinical (unspecified phase)
0.6727	Remote Similarity	NPD8994	Approved
0.64	Remote Similarity	NPD9051	Approved
0.64	Remote Similarity	NPD9053	Approved
0.64	Remote Similarity	NPD9052	Approved
0.5926	Remote Similarity	NPD9055	Approved
0.5926	Remote Similarity	NPD9056	Approved
0.5818	Remote Similarity	NPD8995	Clinical (unspecified phase)
0.5818	Remote Similarity	NPD8996	Phase 3
0.58	Remote Similarity	NPD8814	Phase 3
0.5645	Remote Similarity	NPD904	Phase 3
0.5645	Remote Similarity	NPD1399	Approved
0.5645	Remote Similarity	NPD1400	Approved
0.5645	Remote Similarity	NPD905	Approved
0.5614	Remote Similarity	NPD8958	Phase 2
0.5614	Remote Similarity	NPD8957	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