NPASS Compound

Structure

NPC478999 OpenBabel06302215142D 37 40 0 0 1 0 0 0 0 0999 V2000 -1.2601 -1.2601 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3090 -0.9511 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 -1.5388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3090 -0.9511 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.0000 -0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.5509 0.8346 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5469 0.9242 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2379 0.2014 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1037 -0.7895 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.9771 -1.2765 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.8505 -1.7635 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7239 -2.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7090 -1.2506 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9921 -2.2764 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.1336 -2.7893 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.2602 -2.3023 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.4018 -2.8152 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2453 -1.3024 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6656 -0.3951 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1486 -3.7892 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2901 -4.3021 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4167 -3.8151 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3051 -5.3020 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1785 -5.7890 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1935 -6.7889 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3350 -7.3018 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3500 -8.3016 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4915 -8.8145 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0070 -3.2763 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8804 -3.7633 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8954 -4.7632 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7389 -3.2504 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8982 1.8604 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8847 2.0243 0.0000 O 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 -0.5878 0.8090 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7689 0.6394 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 35 1 0 0 0 0 2 3 2 0 0 0 0 4 3 1 6 0 0 0 4 5 1 0 0 0 0 4 18 1 0 0 0 0 5 6 1 0 0 0 0 5 35 1 0 0 0 0 5 37 1 6 0 0 0 6 7 1 0 0 0 0 7 8 2 0 0 0 0 7 33 1 0 0 0 0 9 8 1 1 0 0 0 9 10 1 0 0 0 0 9 18 1 0 0 0 0 10 11 1 6 0 0 0 10 14 1 0 0 0 0 11 12 1 0 0 0 0 11 13 1 0 0 0 0 11 14 1 0 0 0 0 14 15 1 0 0 0 0 14 29 1 1 0 0 0 15 16 1 0 0 0 0 15 20 1 6 0 0 0 16 17 1 1 0 0 0 16 18 1 0 0 0 0 18 19 1 1 0 0 0 20 21 1 0 0 0 0 21 22 2 0 0 0 0 21 23 1 0 0 0 0 23 24 2 0 0 0 0 24 25 1 0 0 0 0 25 26 2 0 0 0 0 26 27 1 0 0 0 0 27 28 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 33 34 1 0 0 0 0 35 36 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	514.22
Volume:	516.639
LogP:	1.796
LogD:	0.878
LogS:	-4.121
# Rotatable Bonds:	8
TPSA:	147.43
# H-Bond Aceptor:	9
# H-Bond Donor:	3
# Rings:	4
# Heavy Atoms:	9

MedChem Properties

QED Drug-Likeness Score:	0.157
Synthetic Accessibility Score:	5.357
Fsp3:	0.571
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.938
MDCK Permeability:	3.378179462742992e-05
Pgp-inhibitor:	0.007
Pgp-substrate:	0.778
Human Intestinal Absorption (HIA):	0.797
20% Bioavailability (F20%):	0.022
30% Bioavailability (F30%):	0.626

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.443
Plasma Protein Binding (PPB):	32.549381256103516%
Volume Distribution (VD):	0.975
Pgp-substrate:	37.010475158691406%

ADMET: Metabolism

CYP1A2-inhibitor:	0.054
CYP1A2-substrate:	0.078
CYP2C19-inhibitor:	0.072
CYP2C19-substrate:	0.082
CYP2C9-inhibitor:	0.12
CYP2C9-substrate:	0.318
CYP2D6-inhibitor:	0.237
CYP2D6-substrate:	0.226
CYP3A4-inhibitor:	0.473
CYP3A4-substrate:	0.171

ADMET: Excretion

Clearance (CL):	1.627
Half-life (T1/2):	0.293

ADMET: Toxicity

hERG Blockers:	0.521
Human Hepatotoxicity (H-HT):	0.942
Drug-inuced Liver Injury (DILI):	0.113
AMES Toxicity:	0.141
Rat Oral Acute Toxicity:	0.943
Maximum Recommended Daily Dose:	0.964
Skin Sensitization:	0.89
Carcinogencity:	0.494
Eye Corrosion:	0.004
Eye Irritation:	0.017
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: NPC478999

Natural Product ID:	NPC478999
*Common Name:**	RMEVRZXXPIOHPF-KCTSRLQKSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	RMEVRZXXPIOHPF-KCTSRLQKSA-N
Standard InCHI:	InChI=1S/C28H34O9/c1-15-11-20-26(34,23(15)33)13-18(14-30)12-19-22-25(4,5)28(22,37-17(3)31)24(16(2)27(19,20)35)36-21(32)9-7-6-8-10-29/h6-12,16,19-20,22,24,30,34-35H,13-14H2,1-5H3/b8-6+,9-7+/t16-,19+,20-,22-,24-,26-,27-,28-/m1/s1
SMILES:	CC1=C[C@@H]2[C@](CC(=C[C@H]3[C@@H]4C(C)(C)[C@@]4([C@@H]([C@@H](C)[C@]23O)OC(=O)/C=C/C=C/C=O)OC(=O)C)CO)(C1=O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	130424064
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds]

*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
NPO1692	Aquilaria malaccensis	Species	Thymelaeaceae	Eukaryota	Seeds	n.a.	n.a.	PMID[28445049]
NPO1692	Aquilaria malaccensis	Species	Thymelaeaceae	Eukaryota	Agarwood	n.a.	n.a.	PMID[29083898]
NPO1692	Aquilaria malaccensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30672698]
NPO1692	Aquilaria malaccensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7320738]
NPO1692	Aquilaria malaccensis	Species	Thymelaeaceae	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	1

Activity Type	# Activity
Cell Line	5

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT82	Cell Line	MDA-MB-231	Homo sapiens	IC50	>	10000.0	nM	PMID[28445049]
NPT65	Cell Line	HepG2	Homo sapiens	IC50	>	10000.0	nM	PMID[28445049]
NPT81	Cell Line	A549	Homo sapiens	IC50	>	10000.0	nM	PMID[28445049]
NPT2740	Cell Line	Neutrophils		Activity	=	106.1	%	PMID[28445049]
NPT2740	Cell Line	Neutrophils		IC50	=	2700.0	nM	PMID[28445049]

☑ 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 NPC478999 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	244
0.1-0.2	1363
0.2-0.3	4053
0.3-0.4	6586
0.4-0.5	13859
0.5-0.6	9939
0.6-0.7	5404
0.7-0.8	1080
0.8-0.85	49
0.85-0.9	48
0.9-0.95	58
0.95-1	14

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 NPC478999 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	223
0.1-0.2	1639
0.2-0.3	3534
0.3-0.4	2383
0.4-0.5	906
0.5-0.6	318
0.6-0.7	138
0.7-0.8	9
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

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