NPASS Compound

Structure

CID326966 OpenBabel06191716192D 40 41 0 0 1 0 0 0 0 0999 V2000 7.7942 4.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9282 6.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.2583 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.2583 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.3923 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.3923 2.0000 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 0.8660 -1.5000 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 -0.0000 -1.0000 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 6.0622 4.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6603 2.0000 0.0000 C 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 6.0622 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9282 5.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5263 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 -0.0000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -2.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 7.7942 1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 6.0622 3.5000 0.0000 C 0 0 1 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 6.9282 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9282 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -3.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 -0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 -2.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 7.7942 0.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 6.9282 3.0000 0.0000 N 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 6.0622 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9282 -1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -4.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 3.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 2.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 17 1 0 0 0 0 2 17 1 0 0 0 0 3 4 2 0 0 0 0 3 5 1 0 0 0 0 4 6 1 0 0 0 0 5 7 2 0 0 0 0 6 18 2 0 0 0 0 7 18 1 0 0 0 0 8 10 1 0 0 0 0 8 19 2 0 0 0 0 9 11 2 0 0 0 0 9 19 1 0 0 0 0 10 20 2 0 0 0 0 11 20 1 0 0 0 0 12 17 1 0 0 0 0 13 19 1 0 0 0 0 13 21 1 0 0 0 0 14 18 1 0 0 0 0 15 24 1 0 0 0 0 15 31 1 0 0 0 0 16 25 1 0 0 0 0 16 30 1 0 0 0 0 20 34 1 0 0 0 0 21 26 1 0 0 0 0 21 29 1 1 0 0 0 22 14 1 6 0 0 0 22 27 1 0 0 0 0 22 32 1 0 0 0 0 23 12 1 6 0 0 0 23 28 1 0 0 0 0 23 33 1 0 0 0 0 24 30 2 3 0 0 0 24 35 1 0 0 0 0 25 32 2 3 0 0 0 25 36 1 0 0 0 0 26 31 2 3 0 0 0 26 37 1 0 0 0 0 27 33 2 3 0 0 0 27 38 1 0 0 0 0 28 39 2 0 0 0 0 28 40 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	555.27
Volume:	563.245
LogP:	0.143
LogD:	0.408
LogS:	-3.013
# Rotatable Bonds:	19
TPSA:	199.95
# H-Bond Aceptor:	12
# H-Bond Donor:	8
# Rings:	2
# Heavy Atoms:	12

MedChem Properties

QED Drug-Likeness Score:	0.157
Synthetic Accessibility Score:	3.293
Fsp3:	0.393
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-6.675
MDCK Permeability:	2.2008034648024477e-05
Pgp-inhibitor:	0.001
Pgp-substrate:	0.807
Human Intestinal Absorption (HIA):	0.091
20% Bioavailability (F20%):	0.159
30% Bioavailability (F30%):	0.888

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.071
Plasma Protein Binding (PPB):	46.52355194091797%
Volume Distribution (VD):	0.287
Pgp-substrate:	53.86415100097656%

ADMET: Metabolism

CYP1A2-inhibitor:	0.004
CYP1A2-substrate:	0.007
CYP2C19-inhibitor:	0.12
CYP2C19-substrate:	0.04
CYP2C9-inhibitor:	0.255
CYP2C9-substrate:	0.149
CYP2D6-inhibitor:	0.006
CYP2D6-substrate:	0.131
CYP3A4-inhibitor:	0.248
CYP3A4-substrate:	0.024

ADMET: Excretion

Clearance (CL):	3.824
Half-life (T1/2):	0.893

ADMET: Toxicity

hERG Blockers:	0.134
Human Hepatotoxicity (H-HT):	0.101
Drug-inuced Liver Injury (DILI):	0.015
AMES Toxicity:	0.007
Rat Oral Acute Toxicity:	0.106
Maximum Recommended Daily Dose:	0.025
Skin Sensitization:	0.195
Carcinogencity:	0.036
Eye Corrosion:	0.003
Eye Irritation:	0.01
Respiratory Toxicity:	0.058

Download Data

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

Natural Product: NPC326966

Natural Product ID:	NPC326966
*Common Name:**	Enkephalin
IUPAC Name:	(2S)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoic acid
Synonyms:	Enkephalin; Leu-enkephalin; Leucine- enkephalin
Standard InCHIKey:	URLZCHNOLZSCCA-VABKMULXSA-N
Standard InCHI:	InChI=1S/C28H37N5O7/c1-17(2)12-23(28(39)40)33-27(38)22(14-18-6-4-3-5-7-18)32-25(36)16-30-24(35)15-31-26(37)21(29)13-19-8-10-20(34)11-9-19/h3-11,17,21-23,34H,12-16,29H2,1-2H3,(H,30,35)(H,31,37)(H,32,36)(H,33,38)(H,39,40)/t21-,22-,23-/m0/s1
SMILES:	CC(C)CC(C(=O)O)NC(=O)C(CC1=CC=CC=C1)NC(=O)CNC(=O)CNC(=O)C(CC2=CC=C(C=C2)O)N
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL8234
PubChem CID:	461776
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:0000348] Peptides [CHEMONTID:0004831] Oligopeptides

*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

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Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO1797	Homo sapiens	Species	Hominidae	Eukaryota	n.a.	blood	n.a.	PMID[9949311]
NPO1797	Homo sapiens	Species	Hominidae	Eukaryota	n.a.	blood	n.a.	PMID[9892086]
NPO1797	Homo sapiens	Species	Hominidae	Eukaryota	n.a.	cerebrospinal fluid	n.a.	PMID[9870205]
NPO1797	Homo sapiens	Species	Hominidae	Eukaryota	n.a.	urine	n.a.	PMID[9869364]
NPO1797	Homo sapiens	Species	Hominidae	Eukaryota	n.a.	urine	n.a.	PMID[9869358]
NPO1797	Homo sapiens	Species	Hominidae	Eukaryota	n.a.	blood	n.a.	PMID[9861496]
NPO1797	Homo sapiens	Species	Hominidae	Eukaryota	n.a.	cerebrospinal fluid	n.a.	PMID[9861478]
NPO1797	Homo sapiens	Species	Hominidae	Eukaryota	n.a.	urine	n.a.	PMID[9857238]
NPO1797	Homo sapiens	Species	Hominidae	Eukaryota	n.a.	urine	n.a.	PMID[9851755]
NPO1797	Homo sapiens	Species	Hominidae	Eukaryota	n.a.	cerebrospinal fluid	n.a.	PMID[9818465]

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☑ 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

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Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference
No data available in table

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☑ 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	12
ED50	1
IC50	34
Kd	1
Ki	49
Others	1138
Potency	4

Activity Type	# Activity
Cell Line	1039
Individual Protein	115
NON-MOLECULAR	2
Organism	35
Others	39
Protein Family	4
Protein-Protein Interaction	1
SINGLE PROTEIN	3
Tissue	1

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Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1167	Individual Protein	Delta opioid receptor	Mus musculus	Ki	=	6.3	nM	PMID[558058]
NPT1167	Individual Protein	Delta opioid receptor	Mus musculus	EC50	=	74.0	nM	PMID[558058]
NPT271	Individual Protein	Delta opioid receptor	Homo sapiens	EC50	=	0.08	nM	PMID[558058]
NPT145	Individual Protein	Mu opioid receptor	Homo sapiens	EC50	=	1.3	nM	PMID[558058]
NPT272	Individual Protein	Kappa opioid receptor	Homo sapiens	EC50	=	80.0	nM	PMID[558058]
NPT1167	Individual Protein	Delta opioid receptor	Mus musculus	Ki	=	6.9	nM	PMID[558058]
NPT2553	Individual Protein	Aminopeptidase N	Homo sapiens	T1/2	=	0.0115	hr	PMID[558058]
NPT27	Others	Unspecified	""	T1/2	=	0.07667	hr	PMID[558058]
NPT2	Others	Unspecified	""	Ratio EC50	=	16.0	n.a.	PMID[558058]
NPT2	Others	Unspecified	""	Ratio EC50	=	1000.0	n.a.	PMID[558058]

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☑ 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 NPC326966 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	134
0.1-0.2	857
0.2-0.3	4376
0.3-0.4	12659
0.4-0.5	9943
0.5-0.6	12153
0.6-0.7	2111
0.7-0.8	391
0.8-0.85	53
0.85-0.9	15
0.9-0.95	3
0.95-1	2

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Similarity Score	Similarity Level	Natural Product ID
0.952	High Similarity	NPC325651
0.9024	High Similarity	NPC283760
0.9	High Similarity	NPC244866
0.896	High Similarity	NPC27581
0.872	High Similarity	NPC319950

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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 NPC326966 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	106
0.1-0.2	424
0.2-0.3	803
0.3-0.4	1790
0.4-0.5	2855
0.5-0.6	2308
0.6-0.7	741
0.7-0.8	109
0.8-0.85	7
0.85-0.9	4
0.9-0.95	3
0.95-1	0

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Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9291	High Similarity	NPD3136	Phase 2
0.9237	High Similarity	NPD6866	Clinical (unspecified phase)
0.9237	High Similarity	NPD6867	Clinical (unspecified phase)
0.8881	High Similarity	NPD7450	Phase 2
0.876	High Similarity	NPD7451	Discontinued

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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