NPASS Compound

Structure

NPC483137 OpenBabel06302215292D 29 31 0 0 1 0 0 0 0 0999 V2000 3.4641 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.3301 0.5000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.4347 1.4945 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4128 1.7024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9128 0.8364 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 6.9073 0.7319 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 7.3141 -0.1817 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 8.3086 -0.2862 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7153 -1.1997 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1275 -2.0088 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1330 -1.9042 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5452 -2.7132 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7263 -0.9907 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.4951 1.5409 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2437 0.0933 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 0.5000 0.0000 O 0 0 0 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 0.8660 0.5000 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 -0.8660 -1.5000 0.0000 C 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 -1.7321 -0.0000 0.0000 C 0 0 0 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 0.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 0.5000 0.0000 O 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 2 1 1 6 0 0 0 2 17 1 0 0 0 0 3 2 1 6 0 0 0 3 4 1 0 0 0 0 3 16 1 0 0 0 0 4 5 1 0 0 0 0 5 6 1 0 0 0 0 6 7 1 6 0 0 0 6 16 1 0 0 0 0 7 15 1 6 0 0 0 8 7 1 1 0 0 0 8 9 1 0 0 0 0 8 14 1 0 0 0 0 9 10 1 0 0 0 0 10 11 2 0 0 0 0 11 12 1 0 0 0 0 12 13 2 0 0 0 0 12 14 1 0 0 0 0 17 18 1 0 0 0 0 18 19 2 0 0 0 0 18 20 1 0 0 0 0 20 21 2 0 0 0 0 21 22 1 0 0 0 0 22 27 2 0 0 0 0 22 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 25 28 1 0 0 0 0 26 27 1 0 0 0 0 28 29 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	402.17
Volume:	406.475
LogP:	3.461
LogD:	2.874
LogS:	-4.153
# Rotatable Bonds:	8
TPSA:	91.29
# H-Bond Aceptor:	7
# H-Bond Donor:	1
# Rings:	3
# Heavy Atoms:	7

MedChem Properties

QED Drug-Likeness Score:	0.425
Synthetic Accessibility Score:	4.41
Fsp3:	0.455
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
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:	-4.7
MDCK Permeability:	4.89260237372946e-05
Pgp-inhibitor:	0.291
Pgp-substrate:	0.005
Human Intestinal Absorption (HIA):	0.173
20% Bioavailability (F20%):	0.013
30% Bioavailability (F30%):	0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.429
Plasma Protein Binding (PPB):	93.74687194824219%
Volume Distribution (VD):	1.355
Pgp-substrate:	5.697272300720215%

ADMET: Metabolism

CYP1A2-inhibitor:	0.606
CYP1A2-substrate:	0.211
CYP2C19-inhibitor:	0.608
CYP2C19-substrate:	0.411
CYP2C9-inhibitor:	0.556
CYP2C9-substrate:	0.023
CYP2D6-inhibitor:	0.079
CYP2D6-substrate:	0.102
CYP3A4-inhibitor:	0.914
CYP3A4-substrate:	0.265

ADMET: Excretion

Clearance (CL):	13.111
Half-life (T1/2):	0.811

ADMET: Toxicity

hERG Blockers:	0.02
Human Hepatotoxicity (H-HT):	0.485
Drug-inuced Liver Injury (DILI):	0.869
AMES Toxicity:	0.278
Rat Oral Acute Toxicity:	0.1
Maximum Recommended Daily Dose:	0.125
Skin Sensitization:	0.692
Carcinogencity:	0.618
Eye Corrosion:	0.004
Eye Irritation:	0.045
Respiratory Toxicity:	0.038

Download Data

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

Natural Product: NPC483137

Natural Product ID:	NPC483137
*Common Name:**	PRXVDDVCKQCKQP-IZONMWRVSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	PRXVDDVCKQCKQP-IZONMWRVSA-N
Standard InCHI:	InChI=1S/C22H26O7/c1-14(27-21(24)13-8-15-6-9-16(26-2)10-7-15)17-11-12-19(28-17)22(25)18-4-3-5-20(23)29-18/h3,5-10,13-14,17-19,22,25H,4,11-12H2,1-2H3/b13-8-/t14-,17-,18+,19+,22+/m0/s1
SMILES:	C[C@@H]([C@@H]1CC[C@H]([C@@H]([C@H]2CC=CC(=O)O2)O)O1)OC(=O)/C=Cc1ccc(cc1)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	n.a.
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000476] Cinnamic acids and derivatives [CHEMONTID:0003480] Cinnamic acid esters

*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
NPO25696	Hyptis brevipes	Species	Lamiaceae	Eukaryota	Whole Plant	Tawangmangu village, Karanganyar, Central Java, Indonesia	2003-FEB	PMID[19422206]
NPO25696	Hyptis brevipes	Species	Lamiaceae	Eukaryota	n.a.	whole plant	n.a.	PMID[19422206]
NPO25696	Hyptis brevipes	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23282042]
NPO25696	Hyptis brevipes	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28099005]
NPO25696	Hyptis brevipes	Species	Lamiaceae	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	6

Activity Type	# Activity
Cell Line	6

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT148	Cell Line	HCT-15	Homo sapiens	IC50	>	10000.0	nM	PMID[28099005]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	>	10000.0	nM	PMID[28099005]
NPT91	Cell Line	KB	Homo sapiens	IC50	=	9500.0	nM	PMID[28099005]
NPT306	Cell Line	PC-3	Homo sapiens	IC50	=	10000.0	nM	PMID[28099005]
NPT165	Cell Line	HeLa	Homo sapiens	IC50	=	4200.0	nM	PMID[28099005]
NPT1171	Cell Line	HEp-2	Homo sapiens	IC50	>	10000.0	nM	PMID[28099005]

☑ 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 NPC483137 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	226
0.1-0.2	1020
0.2-0.3	2779
0.3-0.4	7601
0.4-0.5	10819
0.5-0.6	5948
0.6-0.7	11123
0.7-0.8	3055
0.8-0.85	119
0.85-0.9	3
0.9-0.95	2
0.95-1	2

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 NPC483137 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	196
0.1-0.2	691
0.2-0.3	1602
0.3-0.4	2582
0.4-0.5	2123
0.5-0.6	1214
0.6-0.7	650
0.7-0.8	90
0.8-0.85	2
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