NPASS Compound

Structure

NPC277993 OpenBabel07101719142D 23 24 0 0 1 0 0 0 0 0999 V2000 2.5981 2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3660 -1.3660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3660 -1.3660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8660 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5000 1.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 0.1340 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5000 0.1340 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 1.8660 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 1.7321 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0000 1.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.7321 -0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5000 1.8660 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8660 1.5000 0.0000 C 0 0 1 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 -3.0000 1.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0000 1.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5981 -0.5000 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 -3.0000 2.7321 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 -3.8660 0.5000 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 4.0000 0.0000 O 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 -0.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 10 1 0 0 0 0 2 15 1 0 0 0 0 3 15 1 0 0 0 0 6 7 1 0 0 0 0 7 16 1 0 0 0 0 8 11 1 0 0 0 0 8 13 1 0 0 0 0 9 12 1 0 0 0 0 9 14 1 0 0 0 0 10 21 2 0 0 0 0 10 22 1 0 0 0 0 11 6 1 6 0 0 0 11 17 1 0 0 0 0 12 15 1 0 0 0 0 12 18 1 6 0 0 0 13 16 1 6 0 0 0 13 19 1 0 0 0 0 14 17 1 1 0 0 0 14 22 1 0 0 0 0 15 23 1 0 0 0 0 16 4 1 6 0 0 0 16 20 1 0 0 0 0 17 5 1 6 0 0 0 17 23 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	472.0
Volume:	362.988
LogP:	5.065
LogD:	4.271
LogS:	-4.823
# Rotatable Bonds:	3
TPSA:	35.53
# H-Bond Aceptor:	3
# H-Bond Donor:	0
# Rings:	2
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.408
Synthetic Accessibility Score:	4.857
Fsp3:	0.941
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:	-4.543
MDCK Permeability:	1.718972998787649e-05
Pgp-inhibitor:	0.999
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.03
20% Bioavailability (F20%):	0.095
30% Bioavailability (F30%):	0.93

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.667
Plasma Protein Binding (PPB):	96.26444244384766%
Volume Distribution (VD):	1.731
Pgp-substrate:	7.879044055938721%

ADMET: Metabolism

CYP1A2-inhibitor:	0.336
CYP1A2-substrate:	0.325
CYP2C19-inhibitor:	0.41
CYP2C19-substrate:	0.852
CYP2C9-inhibitor:	0.933
CYP2C9-substrate:	0.091
CYP2D6-inhibitor:	0.006
CYP2D6-substrate:	0.264
CYP3A4-inhibitor:	0.631
CYP3A4-substrate:	0.828

ADMET: Excretion

Clearance (CL):	3.033
Half-life (T1/2):	0.172

ADMET: Toxicity

hERG Blockers:	0.06
Human Hepatotoxicity (H-HT):	0.782
Drug-inuced Liver Injury (DILI):	0.83
AMES Toxicity:	0.162
Rat Oral Acute Toxicity:	0.27
Maximum Recommended Daily Dose:	0.661
Skin Sensitization:	0.658
Carcinogencity:	0.43
Eye Corrosion:	0.977
Eye Irritation:	0.865
Respiratory Toxicity:	0.981

Download Data

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

Natural Product: NPC277993

Natural Product ID:	NPC277993
*Common Name:**	Acetylcaespitol
IUPAC Name:	[(2S,3S,5S)-5-bromo-2-[(1R,3R,4R)-3-bromo-4-chloro-4-methylcyclohexyl]-2,6,6-trimethyloxan-3-yl] acetate
Synonyms:	Acetylcaespitol
Standard InCHIKey:	PVGGMHHFCWKSQT-JQBKIFNJSA-N
Standard InCHI:	InChI=1S/C17H27Br2ClO3/c1-10(21)22-14-9-12(18)15(2,3)23-17(14,5)11-6-7-16(4,20)13(19)8-11/h11-14H,6-9H2,1-5H3/t11-,12+,13-,14+,16-,17+/m1/s1
SMILES:	CC(=O)O[C@H]1C[C@@H](C(C)(C)O[C@@]1(C)[C@@H]1CC[C@](C)([C@@H](C1)Br)Cl)Br
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1087034
PubChem CID:	46881068
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000267] Organohalogen compounds [CHEMONTID:0002867] Alkyl halides [CHEMONTID:0004485] Cyclohexyl halides

*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
NPO29486	Laurencia catarinensis	Species	Rhodomelaceae	Eukaryota	n.a.	Brazilian	n.a.	PMID[20039643]
NPO29486	Laurencia catarinensis	Species	Rhodomelaceae	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

Activity Type	# Activity
Cell Line	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT139	Cell Line	HT-29	Homo sapiens	IC50	=	16100.0	nM	PMID[500853]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	17600.0	nM	PMID[500853]
NPT762	Cell Line	A-431	Homo sapiens	IC50	=	17400.0	nM	PMID[500853]

☑ 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 NPC277993 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	406
0.1-0.2	5666
0.2-0.3	19444
0.3-0.4	10211
0.4-0.5	6549
0.5-0.6	390
0.6-0.7	18
0.7-0.8	3
0.8-0.85	3
0.85-0.9	4
0.9-0.95	1
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC33876
0.9189	High Similarity	NPC469580
0.8904	High Similarity	NPC469581
0.8718	High Similarity	NPC469556
0.8608	High Similarity	NPC469555
0.8493	Intermediate Similarity	NPC83368
0.8088	Intermediate Similarity	NPC308569
0.8088	Intermediate Similarity	NPC469572
0.8088	Intermediate Similarity	NPC469582
0.7564	Intermediate Similarity	NPC150938
0.7123	Intermediate Similarity	NPC469573
0.6854	Remote Similarity	NPC76909
0.6782	Remote Similarity	NPC282598
0.6582	Remote Similarity	NPC475786
0.6429	Remote Similarity	NPC291724
0.6429	Remote Similarity	NPC274261
0.6353	Remote Similarity	NPC244002
0.6265	Remote Similarity	NPC123122
0.6186	Remote Similarity	NPC475934
0.6154	Remote Similarity	NPC469570
0.6154	Remote Similarity	NPC48210
0.6136	Remote Similarity	NPC15714
0.6023	Remote Similarity	NPC83436
0.6	Remote Similarity	NPC237510
0.6	Remote Similarity	NPC472945
0.6	Remote Similarity	NPC472944
0.6	Remote Similarity	NPC475793
0.5978	Remote Similarity	NPC93616
0.5974	Remote Similarity	NPC185116
0.5914	Remote Similarity	NPC246347
0.5914	Remote Similarity	NPC279260
0.5904	Remote Similarity	NPC253123
0.5897	Remote Similarity	NPC204173
0.5882	Remote Similarity	NPC470526
0.5882	Remote Similarity	NPC476718
0.5862	Remote Similarity	NPC30575
0.5854	Remote Similarity	NPC476928
0.5851	Remote Similarity	NPC471377
0.5851	Remote Similarity	NPC280810
0.5843	Remote Similarity	NPC476603
0.5783	Remote Similarity	NPC301725
0.5773	Remote Similarity	NPC469538
0.5765	Remote Similarity	NPC470173
0.5698	Remote Similarity	NPC109510
0.5696	Remote Similarity	NPC472021
0.5682	Remote Similarity	NPC136424
0.5682	Remote Similarity	NPC476606
0.5667	Remote Similarity	NPC477287
0.5641	Remote Similarity	NPC240206
0.5618	Remote Similarity	NPC476719
0.561	Remote Similarity	NPC469926
0.5604	Remote Similarity	NPC471217
0.5604	Remote Similarity	NPC471216
0.5604	Remote Similarity	NPC472943
0.5604	Remote Similarity	NPC472951

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 NPC277993 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	454
0.1-0.2	4724
0.2-0.3	3013
0.3-0.4	692
0.4-0.5	249
0.5-0.6	18
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
0.5679	Remote Similarity	NPD371	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