NPASS Compound

Structure

CID325098 OpenBabel06191716182D 21 23 0 0 1 0 0 0 0 0999 V2000 -0.5013 -2.1706 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8378 -4.5070 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7662 -4.1353 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0906 -4.8787 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8983 -3.0032 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9085 0.3678 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4850 -0.9091 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4582 -1.8888 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.9085 -3.1455 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.8983 0.2255 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.4850 -1.8686 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.6541 -0.4293 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.6541 -2.3483 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.9989 -0.0476 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4582 -0.8888 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.2329 -5.8685 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 3.3137 1.1352 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 5.3510 -2.3686 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 0.9989 -2.7301 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9358 -1.3888 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 2 3 2 0 0 0 0 2 4 2 0 0 0 0 4 16 1 0 0 0 0 5 9 1 0 0 0 0 6 10 1 0 0 0 0 7 11 1 0 0 0 0 8 1 1 1 0 0 0 8 15 1 0 0 0 0 8 19 1 0 0 0 0 9 3 1 6 0 0 0 9 19 1 0 0 0 0 10 12 1 0 0 0 0 10 17 1 6 0 0 0 11 13 1 0 0 0 0 11 18 1 1 0 0 0 12 7 1 6 0 0 0 12 20 1 0 0 0 0 13 5 1 1 0 0 0 13 20 1 0 0 0 0 14 6 1 6 0 0 0 14 15 1 0 0 0 0 14 21 1 0 0 0 0 15 21 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	439.94
Volume:	317.203
LogP:	4.843
LogD:	3.913
LogS:	-4.735
# Rotatable Bonds:	1
TPSA:	30.99
# H-Bond Aceptor:	3
# H-Bond Donor:	0
# Rings:	3
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.351
Synthetic Accessibility Score:	6.858
Fsp3:	0.8
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.668
MDCK Permeability:	1.3793400285067037e-05
Pgp-inhibitor:	0.996
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.005
20% Bioavailability (F20%):	0.01
30% Bioavailability (F30%):	0.652

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.326
Plasma Protein Binding (PPB):	94.94603729248047%
Volume Distribution (VD):	1.748
Pgp-substrate:	1.9666416645050049%

ADMET: Metabolism

CYP1A2-inhibitor:	0.073
CYP1A2-substrate:	0.127
CYP2C19-inhibitor:	0.033
CYP2C19-substrate:	0.885
CYP2C9-inhibitor:	0.064
CYP2C9-substrate:	0.047
CYP2D6-inhibitor:	0.001
CYP2D6-substrate:	0.143
CYP3A4-inhibitor:	0.41
CYP3A4-substrate:	0.891

ADMET: Excretion

Clearance (CL):	2.328
Half-life (T1/2):	0.279

ADMET: Toxicity

hERG Blockers:	0.842
Human Hepatotoxicity (H-HT):	0.626
Drug-inuced Liver Injury (DILI):	0.958
AMES Toxicity:	0.388
Rat Oral Acute Toxicity:	0.145
Maximum Recommended Daily Dose:	0.589
Skin Sensitization:	0.972
Carcinogencity:	0.345
Eye Corrosion:	0.985
Eye Irritation:	0.867
Respiratory Toxicity:	0.957

Download Data

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

Natural Product: NPC325098

Natural Product ID:	NPC325098
*Common Name:**	KKVLDYZJUNUWNP-WBMUAMOFSA-N
IUPAC Name:	n.a.
Synonyms:	12-Epoxyobtusallene Iv
Standard InCHIKey:	KKVLDYZJUNUWNP-WBMUAMOFSA-N
Standard InCHI:	InChI=1S/C15H19Br2ClO3/c1-8-15-14(21-15)6-10(17)12-7-11(18)13(20-12)5-9(19-8)3-2-4-16/h3-4,8-15H,5-7H2,1H3/t2?,8-,9-,10-,11+,12-,13+,14+,15+/m0/s1
SMILES:	CC1C2C(O2)CC(C3CC(C(O3)CC(O1)C=C=CBr)Cl)Br
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1765721
PubChem CID:	52936647
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002648] Tetrahydrofurans

*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
NPO30005	Laurencia marilzae	Species	Rhodomelaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21338119]
NPO30005	Laurencia marilzae	Species	Rhodomelaceae	Eukaryota	n.a.	Paraso Floral, Tenerife, Canary Islands	n.a.	PMID[21338119]

☑ 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
GI50	6

Activity Type	# Activity
Cell Line	6

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT179	Cell Line	A2780	Homo sapiens	GI50	>	10.0	ug.mL-1	PMID[510185]
NPT1723	Cell Line	HBL-100	Homo sapiens	GI50	>	10.0	ug.mL-1	PMID[510185]
NPT165	Cell Line	HeLa	Homo sapiens	GI50	>	10.0	ug.mL-1	PMID[510185]
NPT1577	Cell Line	SW1573	Homo sapiens	GI50	>	10.0	ug.mL-1	PMID[510185]
NPT396	Cell Line	T47D	Homo sapiens	GI50	>	10.0	ug.mL-1	PMID[510185]
NPT1183	Cell Line	WiDr	Homo sapiens	GI50	>	10.0	ug.mL-1	PMID[510185]

☑ 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 NPC325098 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	305
0.1-0.2	6835
0.2-0.3	22763
0.3-0.4	10731
0.4-0.5	1975
0.5-0.6	75
0.6-0.7	3
0.7-0.8	7
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
0.8028	Intermediate Similarity	NPC477431
0.7901	Intermediate Similarity	NPC477428
0.7632	Intermediate Similarity	NPC52781
0.7534	Intermediate Similarity	NPC473294
0.7534	Intermediate Similarity	NPC471472
0.7333	Intermediate Similarity	NPC477423
0.6795	Remote Similarity	NPC473306
0.642	Remote Similarity	NPC477422
0.6341	Remote Similarity	NPC477421
0.6329	Remote Similarity	NPC316572
0.625	Remote Similarity	NPC477429
0.625	Remote Similarity	NPC323677
0.6049	Remote Similarity	NPC473453
0.6047	Remote Similarity	NPC473947
0.5909	Remote Similarity	NPC5361
0.5897	Remote Similarity	NPC471460
0.5897	Remote Similarity	NPC271000
0.5714	Remote Similarity	NPC30915
0.5658	Remote Similarity	NPC41180
0.5658	Remote Similarity	NPC152438
0.5652	Remote Similarity	NPC470175
0.5625	Remote Similarity	NPC250836
0.561	Remote Similarity	NPC301725

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 NPC325098 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	340
0.1-0.2	5617
0.2-0.3	2736
0.3-0.4	427
0.4-0.5	29
0.5-0.6	1
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