NPASS Compound

Structure

NPC63893 OpenBabel06302215112D 30 32 0 0 1 0 0 0 0 0999 V2000 2.3904 -1.2044 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7213 -0.4612 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.0303 0.4898 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0085 0.6977 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6776 -0.0454 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6557 0.1625 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6068 -0.1465 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8636 -0.8156 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9648 1.1136 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7431 -0.6691 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3364 -1.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6581 -1.4781 0.0000 C 0 0 0 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 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 -0.5000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.0622 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 -2.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.3301 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 -3.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 -0.0000 0.0000 O 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 -0.8660 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5878 0.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2 1 1 1 0 0 0 2 3 1 0 0 0 0 3 4 1 0 0 0 0 4 5 1 0 0 0 0 5 6 1 0 0 0 0 6 7 1 0 0 0 0 6 8 1 0 0 0 0 6 9 1 0 0 0 0 10 2 1 1 0 0 0 10 11 1 0 0 0 0 10 29 1 0 0 0 0 11 12 1 0 0 0 0 13 12 1 1 0 0 0 13 14 1 0 0 0 0 13 29 1 0 0 0 0 14 15 2 0 0 0 0 14 26 1 0 0 0 0 15 16 1 0 0 0 0 16 17 2 0 0 0 0 17 22 1 0 0 0 0 17 18 1 0 0 0 0 18 19 1 0 0 0 0 19 20 1 0 0 0 0 19 25 1 6 0 0 0 20 21 1 0 0 0 0 21 22 1 0 0 0 0 21 24 1 6 0 0 0 22 23 2 0 0 0 0 26 27 1 0 0 0 0 27 28 1 0 0 0 0 28 29 1 0 0 0 0 29 30 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	416.33
Volume:	468.34
LogP:	4.334
LogD:	4.167
LogS:	-5.02
# Rotatable Bonds:	6
TPSA:	60.69
# H-Bond Aceptor:	3
# H-Bond Donor:	3
# Rings:	3
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.52
Synthetic Accessibility Score:	4.516
Fsp3:	0.778
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.911
MDCK Permeability:	5.235209391685203e-05
Pgp-inhibitor:	0.025
Pgp-substrate:	0.003
Human Intestinal Absorption (HIA):	0.004
20% Bioavailability (F20%):	0.004
30% Bioavailability (F30%):	0.003

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.008
Plasma Protein Binding (PPB):	96.67484283447266%
Volume Distribution (VD):	1.46
Pgp-substrate:	1.1310724020004272%

ADMET: Metabolism

CYP1A2-inhibitor:	0.083
CYP1A2-substrate:	0.211
CYP2C19-inhibitor:	0.208
CYP2C19-substrate:	0.605
CYP2C9-inhibitor:	0.547
CYP2C9-substrate:	0.164
CYP2D6-inhibitor:	0.015
CYP2D6-substrate:	0.072
CYP3A4-inhibitor:	0.668
CYP3A4-substrate:	0.374

ADMET: Excretion

Clearance (CL):	4.128
Half-life (T1/2):	0.093

ADMET: Toxicity

hERG Blockers:	0.375
Human Hepatotoxicity (H-HT):	0.988
Drug-inuced Liver Injury (DILI):	0.621
AMES Toxicity:	0.069
Rat Oral Acute Toxicity:	0.968
Maximum Recommended Daily Dose:	0.993
Skin Sensitization:	0.855
Carcinogencity:	0.035
Eye Corrosion:	0.004
Eye Irritation:	0.056
Respiratory Toxicity:	0.968

Download Data

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

Natural Product: NPC63893

Natural Product ID:	NPC63893
*Common Name:**	GMRQFYUYWCNGIN-PEJFXWBPSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	GMRQFYUYWCNGIN-PEJFXWBPSA-N
Standard InCHI:	InChI=1S/C27H44O3/c1-18(8-6-14-26(3,4)30)23-12-13-24-20(9-7-15-27(23,24)5)10-11-21-16-22(28)17-25(29)19(21)2/h10-11,18,22-25,28-30H,2,6-9,12-17H2,1,3-5H3/b20-10+,21-11-/t18-,22-,23-,24+,25-,27-/m1/s1
SMILES:	C[C@H](CCCC(C)(C)O)[C@H]1CC[C@H]2/C(=C/C=C3/C[C@H](C[C@H](C3=C)O)O)/CCC[C@]12C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	5283741
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001460] Vitamin D and derivatives

*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
NPO15653	Celastrus vulcanicola	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18616221]
NPO15653	Celastrus vulcanicola	Species	Celastraceae	Eukaryota	stems	Montecristo National Park, province of Santa Ana, El Salvador	2004-JUN	PMID[20873773]
NPO15653	Celastrus vulcanicola	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21419633]
NPO15653	Celastrus vulcanicola	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25695368]
NPO14382	Cynthia roretzi	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO10388	Stevia monardaefolia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6588	Anhalonium lewinii	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO15609	Uvaria tonkinensis	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15653	Celastrus vulcanicola	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24704	Tetrachyron orizabensis	Species	Asteraceae	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
EC50	1
Others	1

Activity Type	# Activity
Individual Protein	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT5654	Individual Protein	Vitamin D3 receptor A	Danio rerio	Efficacy	=	100.0	%	PMID[569951]
NPT5654	Individual Protein	Vitamin D3 receptor A	Danio rerio	EC50	=	0.14	nM	PMID[569951]

☑ 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 NPC63893 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	151
0.1-0.2	1149
0.2-0.3	4826
0.3-0.4	15011
0.4-0.5	9732
0.5-0.6	7200
0.6-0.7	3817
0.7-0.8	693
0.8-0.85	91
0.85-0.9	19
0.9-0.95	4
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID

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 NPC63893 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	148
0.1-0.2	1286
0.2-0.3	4199
0.3-0.4	2471
0.4-0.5	608
0.5-0.6	242
0.6-0.7	143
0.7-0.8	20
0.8-0.85	8
0.85-0.9	9
0.9-0.95	9
0.95-1	7

Similarity Score	Similarity Level	Drug ID	Developmental Stage

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