NPASS Compound

Structure

NPC74945 OpenBabel06302215432D 37 42 0 0 1 0 0 0 0 0999 V2000 -2.4048 -3.3261 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7085 -2.3930 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.6684 -2.1894 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.9720 -1.2562 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3157 -0.5267 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3558 -0.7304 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0522 -1.6635 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6995 -0.0008 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8495 -0.4911 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8492 -1.4729 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0006 -1.9635 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8501 -1.4724 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8504 -2.4762 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8498 -0.4906 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6999 0.0005 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5503 -0.4901 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5506 -1.4719 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.7005 -1.9630 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.7008 -2.9442 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5511 -3.4348 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4013 -2.9437 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.4015 -3.9475 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2517 -3.4343 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 5.1006 -2.9432 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1003 -1.9620 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4010 -1.9625 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.4007 -0.9587 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2519 -4.4151 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6511 -5.3109 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9224 -5.9674 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0252 -6.9427 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0730 -5.4772 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2766 -4.5179 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9319 -1.0526 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5882 -1.7821 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3247 -2.9189 0.0000 O 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 2 7 1 0 0 0 0 3 4 1 0 0 0 0 3 37 1 6 0 0 0 4 5 1 0 0 0 0 4 35 1 6 0 0 0 5 6 1 0 0 0 0 6 7 1 0 0 0 0 6 8 1 6 0 0 0 9 8 1 6 0 0 0 9 10 1 0 0 0 0 9 34 1 0 0 0 0 10 11 1 0 0 0 0 11 12 1 0 0 0 0 12 18 1 0 0 0 0 12 13 1 6 0 0 0 12 14 1 0 0 0 0 14 15 1 1 0 0 0 14 34 1 0 0 0 0 15 16 1 0 0 0 0 17 16 1 1 0 0 0 17 18 1 0 0 0 0 17 26 1 0 0 0 0 18 19 1 6 0 0 0 19 20 1 0 0 0 0 20 21 1 0 0 0 0 21 26 1 0 0 0 0 21 22 1 6 0 0 0 21 23 1 0 0 0 0 23 24 1 0 0 0 0 23 28 1 6 0 0 0 24 25 1 0 0 0 0 25 26 1 0 0 0 0 26 27 1 6 0 0 0 28 33 1 0 0 0 0 28 29 2 0 0 0 0 29 30 1 0 0 0 0 30 31 2 0 0 0 0 30 32 1 0 0 0 0 32 33 1 0 0 0 0 35 36 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	518.32
Volume:	532.356
LogP:	4.551
LogD:	3.894
LogS:	-4.826
# Rotatable Bonds:	4
TPSA:	101.52
# H-Bond Aceptor:	7
# H-Bond Donor:	3
# Rings:	6
# Heavy Atoms:	7

MedChem Properties

QED Drug-Likeness Score:	0.476
Synthetic Accessibility Score:	5.18
Fsp3:	0.867
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.988
MDCK Permeability:	2.2942060240893625e-05
Pgp-inhibitor:	0.559
Pgp-substrate:	0.984
Human Intestinal Absorption (HIA):	0.014
20% Bioavailability (F20%):	0.022
30% Bioavailability (F30%):	0.045

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.084
Plasma Protein Binding (PPB):	97.03829193115234%
Volume Distribution (VD):	1.356
Pgp-substrate:	3.5125274658203125%

ADMET: Metabolism

CYP1A2-inhibitor:	0.014
CYP1A2-substrate:	0.883
CYP2C19-inhibitor:	0.018
CYP2C19-substrate:	0.635
CYP2C9-inhibitor:	0.185
CYP2C9-substrate:	0.086
CYP2D6-inhibitor:	0.019
CYP2D6-substrate:	0.328
CYP3A4-inhibitor:	0.544
CYP3A4-substrate:	0.541

ADMET: Excretion

Clearance (CL):	12.466
Half-life (T1/2):	0.115

ADMET: Toxicity

hERG Blockers:	0.789
Human Hepatotoxicity (H-HT):	0.34
Drug-inuced Liver Injury (DILI):	0.123
AMES Toxicity:	0.048
Rat Oral Acute Toxicity:	0.879
Maximum Recommended Daily Dose:	0.972
Skin Sensitization:	0.923
Carcinogencity:	0.244
Eye Corrosion:	0.003
Eye Irritation:	0.014
Respiratory Toxicity:	0.963

Download Data

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

Natural Product: NPC74945

Natural Product ID:	NPC74945
*Common Name:**	YBZZSZQZDODUAA-JCTRZUIWSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	YBZZSZQZDODUAA-JCTRZUIWSA-N
Standard InCHI:	InChI=1S/C30H46O7/c1-17-27(32)24(34-4)15-26(36-17)37-20-7-10-28(2)19(14-20)5-6-23-22(28)8-11-29(3)21(9-12-30(23,29)33)18-13-25(31)35-16-18/h13,17,19-24,26-27,32-33H,5-12,14-16H2,1-4H3/t17-,19+,20-,21+,22-,23+,24+,26-,27-,28-,29+,30-/m0/s1
SMILES:	C[C@H]1[C@@H]([C@@H](C[C@@H](O1)O[C@H]1CC[C@@]2(C)[C@H](CC[C@@H]3[C@@H]2CC[C@]2(C)[C@H](CC[C@]32O)C2=CC(=O)OC2)C1)OC)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	12310596
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001555] Cardenolides and derivatives [CHEMONTID:0001559] Cardenolide glycosides 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
NPO3447	Beaumontia murtonii	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28598616]
NPO40841	Eugenia operculata	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[28598616]
NPO3447	Beaumontia murtonii	Species	Apocynaceae	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	4
Others	4

Activity Type	# Activity
Cell Line	7
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT90	Cell Line	DU-145	Homo sapiens	IC50	=	140.0	nM	PMID[28598616]
NPT393	Cell Line	HCT-116	Homo sapiens	IC50	=	58.0	nM	PMID[28598616]
NPT71	Cell Line	HEK293	Homo sapiens	IC50	=	5000.0	nM	PMID[28598616]
NPT1229	Cell Line	Huh-7	Homo sapiens	Activity	=	80.1	%	PMID[28598616]
NPT1229	Cell Line	Huh-7	Homo sapiens	Activity	=	72.9	%	PMID[28598616]
NPT1229	Cell Line	Huh-7	Homo sapiens	Activity	=	19.9	%	PMID[28598616]
NPT1229	Cell Line	Huh-7	Homo sapiens	Activity	=	27.1	%	PMID[28598616]
NPT2	Others	Unspecified		IC50	=	93.0	nM	PMID[28598616]

☑ 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 NPC74945 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	241
0.1-0.2	1654
0.2-0.3	5030
0.3-0.4	10955
0.4-0.5	10240
0.5-0.6	6368
0.6-0.7	4726
0.7-0.8	2781
0.8-0.85	417
0.85-0.9	144
0.9-0.95	86
0.95-1	55

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 NPC74945 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	207
0.1-0.2	1768
0.2-0.3	4069
0.3-0.4	2075
0.4-0.5	547
0.5-0.6	264
0.6-0.7	171
0.7-0.8	31
0.8-0.85	5
0.85-0.9	1
0.9-0.95	9
0.95-1	3

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