NPASS Compound

Structure

NPC42934 OpenBabel06302216002D 35 34 0 0 1 0 0 0 0 0999 V2000 2.5981 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 4.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 3.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 1.5000 0.0000 C 0 0 1 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 -3.4641 3.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 1.5000 0.0000 O 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 -5.1962 -1.0000 0.0000 C 0 0 0 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 -6.9282 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7942 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 -0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -7.7942 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6603 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5263 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.3923 -0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -10.3923 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5263 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.2583 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.2583 0.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 0.5000 0.0000 O 0 0 0 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 -2.5981 0.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 2.0000 0.0000 O 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 0.8660 0.5000 0.0000 C 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 1 2 1 0 0 0 0 2 3 2 0 0 0 0 2 33 1 0 0 0 0 3 4 1 0 0 0 0 4 5 2 0 0 0 0 4 6 1 0 0 0 0 6 7 1 0 0 0 0 6 32 1 0 0 0 0 7 8 1 0 0 0 0 8 9 1 0 0 0 0 9 10 1 0 0 0 0 10 11 1 0 0 0 0 10 31 1 6 0 0 0 11 12 2 0 0 0 0 11 13 1 0 0 0 0 13 14 1 0 0 0 0 14 15 1 0 0 0 0 15 16 1 0 0 0 0 16 17 2 0 0 0 0 16 30 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 1 0 0 0 0 20 29 1 0 0 0 0 21 22 1 0 0 0 0 22 23 1 0 0 0 0 23 24 1 0 0 0 0 24 25 1 0 0 0 0 24 28 1 1 0 0 0 25 26 2 0 0 0 0 25 27 1 0 0 0 0 33 34 1 0 0 0 0 34 35 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	502.26
Volume:	496.348
LogP:	-3.255
LogD:	-2.699
LogS:	-1.157
# Rotatable Bonds:	20
TPSA:	216.95
# H-Bond Aceptor:	13
# H-Bond Donor:	8
# Rings:	0
# Heavy Atoms:	13

MedChem Properties

QED Drug-Likeness Score:	0.051
Synthetic Accessibility Score:	4.25
Fsp3:	0.636
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	1
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-6.147
MDCK Permeability:	0.0025758615229278803
Pgp-inhibitor:	0.0
Pgp-substrate:	0.73
Human Intestinal Absorption (HIA):	0.994
20% Bioavailability (F20%):	0.263
30% Bioavailability (F30%):	0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.316
Plasma Protein Binding (PPB):	12.770919799804688%
Volume Distribution (VD):	0.658
Pgp-substrate:	90.87918853759766%

ADMET: Metabolism

CYP1A2-inhibitor:	0.002
CYP1A2-substrate:	0.014
CYP2C19-inhibitor:	0.022
CYP2C19-substrate:	0.033
CYP2C9-inhibitor:	0.025
CYP2C9-substrate:	0.269
CYP2D6-inhibitor:	0.047
CYP2D6-substrate:	0.101
CYP3A4-inhibitor:	0.01
CYP3A4-substrate:	0.006

ADMET: Excretion

Clearance (CL):	6.521
Half-life (T1/2):	0.403

ADMET: Toxicity

hERG Blockers:	0.096
Human Hepatotoxicity (H-HT):	0.131
Drug-inuced Liver Injury (DILI):	0.011
AMES Toxicity:	0.05
Rat Oral Acute Toxicity:	0.003
Maximum Recommended Daily Dose:	0.019
Skin Sensitization:	0.895
Carcinogencity:	0.155
Eye Corrosion:	0.003
Eye Irritation:	0.05
Respiratory Toxicity:	0.057

Download Data

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

Natural Product: NPC42934

Natural Product ID:	NPC42934
*Common Name:**	KUXHMHSAZYHINP-QRMUCJMYSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	KUXHMHSAZYHINP-QRMUCJMYSA-N
Standard InCHI:	InChI=1S/C22H38N4O9/c1-15(7-11-27)13-19(28)26(34)10-4-6-18(24)22(32)35-12-8-16(2)14-20(29)25(33)9-3-5-17(23)21(30)31/h13-14,17-18,27,33-34H,3-12,23-24H2,1-2H3,(H,30,31)/b15-13-,16-14-/t17-,18-/m0/s1
SMILES:	C/C(=C/C(=O)N(CCC[C@@H](C(=O)OCC/C(=CC(=O)N(CCC[C@@H](C(=O)O)N)O)/C)N)O)/CCO
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	n.a.
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000347] Amino acids and derivatives [CHEMONTID:0000060] Alpha amino acids and derivatives [CHEMONTID:0000394] Alpha amino 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
NPO20735	Aconitum balfourii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28075	Crataegus sanguinea	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO20735	Aconitum balfourii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28075	Crataegus sanguinea	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28355	Pseudocyphellaria crocata	Species	Lobariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20735	Aconitum balfourii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28075	Crataegus sanguinea	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28249	Macaranga pleiostemon	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27977	Crotalaria verrucosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28692	Pteris undulata	Species	Pteridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28673	Cucumaria echinata	Species	Cucumariidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28547	Arthrocnemum glaucum	Species	Chenopodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28285	Taxus harringtonia	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28657	Incarvillea mairei	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29355	Asaemia axillaris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24825	Colchicum bulbocodium	Species	Colchicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28237	Miconia langsdorffii	Species	Melastomataceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23154	Paysonia grandiflora	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27920	Piper kwashoense	Species	Piperaceae	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

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

☑ 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 NPC42934 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	80
0.1-0.2	2278
0.2-0.3	23811
0.3-0.4	13375
0.4-0.5	2761
0.5-0.6	370
0.6-0.7	16
0.7-0.8	2
0.8-0.85	3
0.85-0.9	1
0.9-0.95	0
0.95-1	0

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 NPC42934 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	63
0.1-0.2	775
0.2-0.3	4782
0.3-0.4	2892
0.4-0.5	558
0.5-0.6	80
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

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