NPASS Compound

Structure

NPC485324 OpenBabel06302215582D 32 35 0 0 1 0 0 0 0 0999 V2000 0.0933 1.7796 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 0.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4781 0.6581 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.5827 -0.3364 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4487 -0.8364 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.3147 -0.3364 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1808 -0.8364 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.1808 0.1636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1808 -1.8364 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 5.0468 -2.3364 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9128 -1.8364 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9128 -0.8364 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 6.7788 -1.3364 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7788 -0.3364 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 6.7788 0.6636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9128 1.1636 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 5.0468 0.6636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1808 1.1636 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0468 -0.3364 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 5.9128 2.1636 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7788 2.6636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6449 2.1636 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7788 3.6636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6449 -0.8364 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6449 -1.8364 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 8.5109 -0.3364 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 9.3769 -0.8364 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3147 -2.3364 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3147 -3.3364 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4487 -1.8364 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6691 -0.7431 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 32 2 0 0 0 0 2 3 1 0 0 0 0 3 4 2 0 0 0 0 4 31 1 0 0 0 0 5 4 1 6 0 0 0 5 6 1 0 0 0 0 5 30 1 0 0 0 0 6 7 1 0 0 0 0 7 19 1 0 0 0 0 7 8 1 1 0 0 0 7 9 1 0 0 0 0 9 10 1 1 0 0 0 9 28 1 0 0 0 0 10 11 1 0 0 0 0 11 12 1 0 0 0 0 12 19 1 0 0 0 0 12 13 1 1 0 0 0 12 14 1 0 0 0 0 14 15 1 0 0 0 0 14 24 1 1 0 0 0 15 16 1 0 0 0 0 16 17 1 0 0 0 0 16 20 1 1 0 0 0 17 18 2 0 0 0 0 19 17 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 24 25 2 0 0 0 0 24 26 1 0 0 0 0 26 27 1 0 0 0 0 28 29 2 0 0 0 0 28 30 1 0 0 0 0 31 32 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	448.18
Volume:	431.339
LogP:	1.718
LogD:	0.649
LogS:	-2.979
# Rotatable Bonds:	5
TPSA:	134.89
# H-Bond Aceptor:	10
# H-Bond Donor:	0
# Rings:	4
# Heavy Atoms:	10

MedChem Properties

QED Drug-Likeness Score:	0.499
Synthetic Accessibility Score:	4.655
Fsp3:	0.727
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:	-5.098
MDCK Permeability:	2.4611606932012364e-05
Pgp-inhibitor:	0.992
Pgp-substrate:	0.007
Human Intestinal Absorption (HIA):	0.007
20% Bioavailability (F20%):	0.005
30% Bioavailability (F30%):	0.064

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.436
Plasma Protein Binding (PPB):	46.10418701171875%
Volume Distribution (VD):	1.606
Pgp-substrate:	53.172691345214844%

ADMET: Metabolism

CYP1A2-inhibitor:	0.015
CYP1A2-substrate:	0.86
CYP2C19-inhibitor:	0.09
CYP2C19-substrate:	0.399
CYP2C9-inhibitor:	0.055
CYP2C9-substrate:	0.045
CYP2D6-inhibitor:	0.005
CYP2D6-substrate:	0.111
CYP3A4-inhibitor:	0.378
CYP3A4-substrate:	0.469

ADMET: Excretion

Clearance (CL):	3.69
Half-life (T1/2):	0.586

ADMET: Toxicity

hERG Blockers:	0.015
Human Hepatotoxicity (H-HT):	0.983
Drug-inuced Liver Injury (DILI):	0.939
AMES Toxicity:	0.016
Rat Oral Acute Toxicity:	0.477
Maximum Recommended Daily Dose:	0.197
Skin Sensitization:	0.186
Carcinogencity:	0.044
Eye Corrosion:	0.008
Eye Irritation:	0.056
Respiratory Toxicity:	0.709

Download Data

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

Natural Product: NPC485324

Natural Product ID:	NPC485324
*Common Name:**	ZSVADCKXEHDXBE-XOKLNVNFSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	ZSVADCKXEHDXBE-XOKLNVNFSA-N
Standard InCHI:	InChI=1S/C22H28N2O8/c1-10-23-18(32-24-10)15-9-22(4)12(20(28)31-15)6-7-21(3)13(19(27)29-5)8-14(30-11(2)25)16(26)17(21)22/h12-15,17H,6-9H2,1-5H3/t12-,13-,14-,15-,17-,21-,22-/m0/s1
SMILES:	Cc1nc([C@@H]2C[C@@]3(C)[C@@H](CC[C@@]4(C)[C@@H](C[C@@H](C(=O)[C@H]34)OC(=O)C)C(=O)OC)C(=O)O2)on1
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	44411794
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001640] Naphthopyrans

*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
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14510607]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15987194]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16441078]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16621556]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16945525]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17190459]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17580847]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21338114]
NPO634	Salvia divinorum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25193297]
NPO634	Salvia divinorum	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
EC50	1
Ki	8
Others	5

Activity Type	# Activity
Individual Protein	12
Others	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT145	Individual Protein	Mu opioid receptor	Homo sapiens	Ki	>	10000.0	nM	PMID[17580847]
NPT271	Individual Protein	Delta opioid receptor	Homo sapiens	Ki	>	10000.0	nM	PMID[17580847]
NPT272	Individual Protein	Kappa opioid receptor	Homo sapiens	Ki	=	56.0	nM	PMID[17580847]
NPT145	Individual Protein	Mu opioid receptor	Homo sapiens	Ki	=	430.0	nM	PMID[17580847]
NPT1069	Individual Protein	Mu opioid receptor	Rattus norvegicus	Ki	>	1000.0	nM	PMID[19211245]
NPT1167	Individual Protein	Delta opioid receptor	Mus musculus	Ki	>	1000.0	nM	PMID[19211245]
NPT272	Individual Protein	Kappa opioid receptor	Homo sapiens	Ki	>	1000.0	nM	PMID[19211245]
NPT272	Individual Protein	Kappa opioid receptor	Homo sapiens	Activity	=	50.0	%	PMID[19211245]
NPT1069	Individual Protein	Mu opioid receptor	Rattus norvegicus	Activity	=	8.0	%	PMID[19211245]
NPT272	Individual Protein	Kappa opioid receptor	Homo sapiens	EC50	>	1000.0	nM	PMID[19211245]
NPT1069	Individual Protein	Mu opioid receptor	Rattus norvegicus	Activity	=	99.0	%	PMID[19211245]
NPT4390	Others	Opioid receptors; mu & kappa	Homo sapiens	Ratio Ki	>	170.0	n.a.	PMID[17580847]
NPT5131	Others	Opioid receptors; delta & kappa	Homo sapiens	Ratio Ki	>	170.0	n.a.	PMID[17580847]

☑ 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 NPC485324 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	304
0.1-0.2	3395
0.2-0.3	19544
0.3-0.4	13838
0.4-0.5	5427
0.5-0.6	187
0.6-0.7	1
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

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 NPC485324 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	154
0.1-0.2	1386
0.2-0.3	5041
0.3-0.4	2208
0.4-0.5	355
0.5-0.6	6
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