NPASS Compound

Structure

NPC1043 OpenBabel06302215592D 22 26 0 0 1 0 0 0 0 0999 V2000 0.8518 -2.8466 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5845 -2.4236 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5845 -1.5775 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3397 -1.1415 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0949 -1.5775 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8501 -1.1416 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 4.2862 -0.3864 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9670 0.1665 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0949 0.1665 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.0950 1.0385 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8502 1.4745 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6054 1.0385 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.6053 0.1664 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8501 -0.2695 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 5.3381 1.4615 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3397 -0.2695 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5845 0.1665 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8293 -0.2695 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8293 -1.1415 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -1.4110 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5126 -0.7055 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 1 0 0 0 0 3 19 2 0 0 0 0 3 4 1 0 0 0 0 4 16 2 0 0 0 0 4 5 1 0 0 0 0 5 6 1 0 0 0 0 6 14 1 0 0 0 0 6 7 1 0 0 0 0 7 8 1 0 0 0 0 9 8 1 1 0 0 0 9 14 1 0 0 0 0 9 10 1 0 0 0 0 9 16 1 0 0 0 0 10 11 2 0 0 0 0 11 12 1 0 0 0 0 12 13 1 0 0 0 0 12 15 1 6 0 0 0 14 13 1 6 0 0 0 16 17 1 0 0 0 0 17 18 2 0 0 0 0 18 22 1 0 0 0 0 18 19 1 0 0 0 0 19 20 1 0 0 0 0 20 21 1 0 0 0 0 21 22 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	301.13
Volume:	295.418
LogP:	1.118
LogD:	0.884
LogS:	-1.856
# Rotatable Bonds:	1
TPSA:	51.16
# H-Bond Aceptor:	5
# H-Bond Donor:	1
# Rings:	5
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.798
Synthetic Accessibility Score:	4.966
Fsp3:	0.529
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.964
MDCK Permeability:	2.1952046154183336e-05
Pgp-inhibitor:	0.001
Pgp-substrate:	0.803
Human Intestinal Absorption (HIA):	0.003
20% Bioavailability (F20%):	0.184
30% Bioavailability (F30%):	0.066

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.997
Plasma Protein Binding (PPB):	32.955413818359375%
Volume Distribution (VD):	2.232
Pgp-substrate:	60.90840148925781%

ADMET: Metabolism

CYP1A2-inhibitor:	0.717
CYP1A2-substrate:	0.887
CYP2C19-inhibitor:	0.486
CYP2C19-substrate:	0.867
CYP2C9-inhibitor:	0.037
CYP2C9-substrate:	0.755
CYP2D6-inhibitor:	0.897
CYP2D6-substrate:	0.773
CYP3A4-inhibitor:	0.885
CYP3A4-substrate:	0.796

ADMET: Excretion

Clearance (CL):	8.838
Half-life (T1/2):	0.521

ADMET: Toxicity

hERG Blockers:	0.06
Human Hepatotoxicity (H-HT):	0.128
Drug-inuced Liver Injury (DILI):	0.041
AMES Toxicity:	0.113
Rat Oral Acute Toxicity:	0.696
Maximum Recommended Daily Dose:	0.951
Skin Sensitization:	0.089
Carcinogencity:	0.862
Eye Corrosion:	0.003
Eye Irritation:	0.013
Respiratory Toxicity:	0.928

Download Data

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

Natural Product: NPC1043

Natural Product ID:	NPC1043
*Common Name:**	VXTCKUJRGBGTEH-RMLVOYDJSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	VXTCKUJRGBGTEH-RMLVOYDJSA-N
Standard InCHI:	InChI=1S/C17H19NO4/c1-20-15-11-8-18-5-4-17(3-2-10(19)6-14(17)18)12(11)7-13-16(15)22-9-21-13/h2-3,7,10,14,19H,4-6,8-9H2,1H3/t10-,14-,17+/m0/s1
SMILES:	COc1c2CN3CC[C@]4(C=C[C@@H](C[C@H]34)O)c2cc2c1OCO2
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	n.a.
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0001775] Amaryllidaceae alkaloids [CHEMONTID:0004123] Crinine- and Haemanthamine-type amaryllidaceae alkaloids

*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
NPO22157	Datura wrightii	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23252848]
NPO22054	Cinchona officinalis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1383.1	Murraya paniculata var. omphalocarpa	Varieties	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22054	Cinchona officinalis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1828	Searsia leptodictya	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13659	Helichrysum asperum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23036	Angelica hirsutiflora	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18476	Lophopetalum toxicum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21442	Elaeocarpus sphaericus	Species	Elaeocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20170	Anthoceros punctatus	Species	Anthocerotaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23120	Clausena suffruticosa	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22157	Datura wrightii	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22054	Cinchona officinalis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22009	Lupinus holosericeus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1383.1	Murraya paniculata var. omphalocarpa	Varieties	Rutaceae	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 NPC1043 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	308
0.1-0.2	1328
0.2-0.3	4377
0.3-0.4	12040
0.4-0.5	6740
0.5-0.6	12048
0.6-0.7	4706
0.7-0.8	909
0.8-0.85	149
0.85-0.9	68
0.9-0.95	22
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 NPC1043 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	185
0.1-0.2	657
0.2-0.3	1000
0.3-0.4	2482
0.4-0.5	2570
0.5-0.6	1569
0.6-0.7	572
0.7-0.8	112
0.8-0.85	1
0.85-0.9	2
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