NPASS Compound

Structure

NPC469581 OpenBabel07101719132D 23 24 0 0 1 0 0 0 0 0999 V2000 -2.6084 -3.6566 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8660 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3660 0.3660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7297 -1.0176 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7355 0.4914 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 -2.5391 -0.0517 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0567 -1.9836 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6425 -3.3978 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8320 -0.7588 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0908 -1.7247 0.0000 C 0 0 1 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 -3.5050 -0.3105 0.0000 C 0 0 2 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 -3.7638 -1.2765 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8660 -0.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7321 -2.0000 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 -4.2121 0.3966 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 -4.4709 -1.9836 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 -0.9354 -4.1049 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3837 -2.4319 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 6 13 1 0 0 0 0 7 17 1 0 0 0 0 8 14 1 0 0 0 0 9 12 1 0 0 0 0 9 16 1 0 0 0 0 10 21 2 0 0 0 0 10 22 1 0 0 0 0 11 8 1 6 0 0 0 11 12 1 0 0 0 0 11 17 1 0 0 0 0 12 22 1 1 0 0 0 13 15 1 0 0 0 0 13 18 1 1 0 0 0 14 16 1 6 0 0 0 14 19 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 1 0 0 0 17 23 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	472.0
Volume:	362.988
LogP:	5.038
LogD:	4.05
LogS:	-5.014
# 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:	4.846
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:	-4.59
MDCK Permeability:	1.4225235645426437e-05
Pgp-inhibitor:	0.998
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.03
20% Bioavailability (F20%):	0.055
30% Bioavailability (F30%):	0.929

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.669
Plasma Protein Binding (PPB):	96.19866943359375%
Volume Distribution (VD):	1.802
Pgp-substrate:	6.920941352844238%

ADMET: Metabolism

CYP1A2-inhibitor:	0.132
CYP1A2-substrate:	0.423
CYP2C19-inhibitor:	0.388
CYP2C19-substrate:	0.903
CYP2C9-inhibitor:	0.93
CYP2C9-substrate:	0.165
CYP2D6-inhibitor:	0.005
CYP2D6-substrate:	0.411
CYP3A4-inhibitor:	0.739
CYP3A4-substrate:	0.91

ADMET: Excretion

Clearance (CL):	2.839
Half-life (T1/2):	0.227

ADMET: Toxicity

hERG Blockers:	0.115
Human Hepatotoxicity (H-HT):	0.505
Drug-inuced Liver Injury (DILI):	0.897
AMES Toxicity:	0.353
Rat Oral Acute Toxicity:	0.131
Maximum Recommended Daily Dose:	0.049
Skin Sensitization:	0.822
Carcinogencity:	0.513
Eye Corrosion:	0.973
Eye Irritation:	0.712
Respiratory Toxicity:	0.964

Download Data

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

Natural Product: NPC469581

Natural Product ID:	NPC469581
*Common Name:**	(5S)-5-Acetoxydeoxycaespitol
IUPAC Name:	[(1S,2S,4R,5R)-4-bromo-2-[(2R,5S)-5-bromo-2,6,6-trimethyloxan-2-yl]-5-chloro-5-methylcyclohexyl] acetate
Synonyms:	(5S)-5-Acetoxydeoxycaespitol
Standard InCHIKey:	FLSDGNYXFPEZAL-WQAPVAGSSA-N
Standard InCHI:	InChI=1S/C17H27Br2ClO3/c1-10(21)22-12-9-16(4,20)14(19)8-11(12)17(5)7-6-13(18)15(2,3)23-17/h11-14H,6-9H2,1-5H3/t11-,12-,13-,14+,16+,17+/m0/s1
SMILES:	CC(=O)O[C@H]1C[C@@](C)(Cl)[C@@H](C[C@@H]1[C@@]1(C)CC[C@@H](C(O1)(C)C)Br)Br
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1088318
PubChem CID:	46881054
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	=	48800.0	nM	PMID[479795]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	52400.0	nM	PMID[479795]
NPT762	Cell Line	A-431	Homo sapiens	IC50	=	54900.0	nM	PMID[479795]

☑ 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 NPC469581 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	429
0.1-0.2	5845
0.2-0.3	20132
0.3-0.4	9903
0.4-0.5	5966
0.5-0.6	394
0.6-0.7	17
0.7-0.8	5
0.8-0.85	0
0.85-0.9	4
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9459	High Similarity	NPC469580
0.8974	High Similarity	NPC469556
0.8904	High Similarity	NPC277993
0.8904	High Similarity	NPC33876
0.8861	High Similarity	NPC469555
0.7857	Intermediate Similarity	NPC469582
0.7857	Intermediate Similarity	NPC308569
0.7857	Intermediate Similarity	NPC469572
0.7564	Intermediate Similarity	NPC83368
0.6933	Remote Similarity	NPC469573
0.6889	Remote Similarity	NPC76909
0.6835	Remote Similarity	NPC475786
0.6818	Remote Similarity	NPC282598
0.6747	Remote Similarity	NPC150938
0.6714	Remote Similarity	NPC291724
0.6714	Remote Similarity	NPC274261
0.6392	Remote Similarity	NPC475934
0.6364	Remote Similarity	NPC204173
0.6235	Remote Similarity	NPC475793
0.6235	Remote Similarity	NPC237510
0.618	Remote Similarity	NPC15714
0.6118	Remote Similarity	NPC123122
0.6067	Remote Similarity	NPC83436
0.6022	Remote Similarity	NPC48210
0.6022	Remote Similarity	NPC469570
0.593	Remote Similarity	NPC476422
0.5909	Remote Similarity	NPC30575
0.5904	Remote Similarity	NPC476928
0.5897	Remote Similarity	NPC240206
0.5851	Remote Similarity	NPC93616
0.5789	Remote Similarity	NPC246347
0.5789	Remote Similarity	NPC475276
0.5789	Remote Similarity	NPC279260
0.5747	Remote Similarity	NPC476718
0.5747	Remote Similarity	NPC109510
0.5729	Remote Similarity	NPC471377
0.5729	Remote Similarity	NPC280810
0.5714	Remote Similarity	NPC329871
0.5714	Remote Similarity	NPC476603
0.5682	Remote Similarity	NPC55508
0.5682	Remote Similarity	NPC71152
0.5682	Remote Similarity	NPC74639
0.5682	Remote Similarity	NPC272359
0.5667	Remote Similarity	NPC244002
0.5663	Remote Similarity	NPC474768
0.5657	Remote Similarity	NPC469538
0.5647	Remote Similarity	NPC301725
0.5638	Remote Similarity	NPC273356
0.5638	Remote Similarity	NPC97491
0.5625	Remote Similarity	NPC9880
0.5625	Remote Similarity	NPC230070
0.5625	Remote Similarity	NPC185116
0.5625	Remote Similarity	NPC87828
0.5618	Remote Similarity	NPC186851

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 NPC469581 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	480
0.1-0.2	4867
0.2-0.3	2963
0.3-0.4	589
0.4-0.5	233
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
		NPD

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