NPASS Compound

Structure

NPC100898 OpenBabel06302215082D 29 32 0 0 1 0 0 0 0 0999 V2000 2.5839 -0.4822 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7090 0.0232 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8339 -0.4817 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8336 -1.4447 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0005 -1.9260 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 -0.0007 -2.8897 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8348 -3.3711 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6691 -2.8893 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3376 -2.8890 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3374 -1.9254 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1718 -1.4436 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0058 -1.9250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0060 -2.8887 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1721 -3.3704 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1723 -4.3334 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3934 -4.8996 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5033 -1.4440 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.6689 -1.9257 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8344 -1.4443 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8341 -0.4813 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0003 1.0104 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8754 1.5153 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8756 2.5257 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7508 3.0306 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8746 1.5158 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8743 2.5261 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7497 1.0108 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6246 1.5162 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 3 2 1 6 0 0 0 3 4 1 0 0 0 0 3 21 1 0 0 0 0 4 5 1 0 0 0 0 5 19 1 0 0 0 0 5 6 1 0 0 0 0 6 7 1 0 0 0 0 7 8 1 0 0 0 0 8 18 2 0 0 0 0 8 9 1 0 0 0 0 9 14 2 0 0 0 0 9 10 1 0 0 0 0 10 11 2 0 0 0 0 10 17 1 0 0 0 0 11 12 1 0 0 0 0 12 13 2 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 17 18 1 0 0 0 0 18 19 1 0 0 0 0 19 20 1 1 0 0 0 20 21 1 0 0 0 0 21 22 1 6 0 0 0 22 23 2 0 0 0 0 22 26 1 0 0 0 0 23 24 1 0 0 0 0 24 25 1 0 0 0 0 26 27 2 0 0 0 0 26 28 1 0 0 0 0 28 29 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	398.22
Volume:	413.474
LogP:	4.13
LogD:	3.752
LogS:	-3.784
# Rotatable Bonds:	6
TPSA:	63.79
# H-Bond Aceptor:	6
# H-Bond Donor:	1
# Rings:	4
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.471
Synthetic Accessibility Score:	4.013
Fsp3:	0.522
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
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:	-4.908
MDCK Permeability:	2.0580755517585203e-05
Pgp-inhibitor:	0.956
Pgp-substrate:	0.854
Human Intestinal Absorption (HIA):	0.003
20% Bioavailability (F20%):	0.005
30% Bioavailability (F30%):	0.012

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.992
Plasma Protein Binding (PPB):	86.442138671875%
Volume Distribution (VD):	1.382
Pgp-substrate:	8.686127662658691%

ADMET: Metabolism

CYP1A2-inhibitor:	0.908
CYP1A2-substrate:	0.965
CYP2C19-inhibitor:	0.864
CYP2C19-substrate:	0.907
CYP2C9-inhibitor:	0.483
CYP2C9-substrate:	0.637
CYP2D6-inhibitor:	0.957
CYP2D6-substrate:	0.896
CYP3A4-inhibitor:	0.922
CYP3A4-substrate:	0.915

ADMET: Excretion

Clearance (CL):	5.387
Half-life (T1/2):	0.485

ADMET: Toxicity

hERG Blockers:	0.963
Human Hepatotoxicity (H-HT):	0.489
Drug-inuced Liver Injury (DILI):	0.575
AMES Toxicity:	0.246
Rat Oral Acute Toxicity:	0.951
Maximum Recommended Daily Dose:	0.986
Skin Sensitization:	0.826
Carcinogencity:	0.936
Eye Corrosion:	0.004
Eye Irritation:	0.023
Respiratory Toxicity:	0.957

Download Data

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

Natural Product: NPC100898

Natural Product ID:	NPC100898
*Common Name:**	LELBFTMXCIIKKX-MYLQJJOTSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	LELBFTMXCIIKKX-MYLQJJOTSA-N
Standard InCHI:	InChI=1S/C23H30N2O4/c1-5-14-12-25-10-9-15-21-18(7-6-8-20(21)28-3)24-22(15)19(25)11-16(14)17(13-27-2)23(26)29-4/h6-8,13-14,16,19,24H,5,9-12H2,1-4H3/b17-13+/t14-,16+,19-/m1/s1
SMILES:	CC[C@@H]1CN2CCc3c4c(cccc4OC)[nH]c3[C@H]2C[C@@H]1/C(=COC)/C(=O)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	15560576
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0002750] Corynanthean-type 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
NPO10533	Ixeris chinensis	Species	Asteraceae	Eukaryota	n.a.	whole plant	n.a.	PMID[15635221]
NPO10533	Ixeris chinensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17067155]
NPO2677	Paralemnalia clavata	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18247571]
NPO1569	Mitragyna speciosa	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23517479]
NPO8554	Cryptocarya lividula	Species	Lauraceae	Eukaryota	n.a.	leaf	n.a.	PMID[27032214]
NPO1569	Mitragyna speciosa	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10533	Ixeris chinensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1569	Mitragyna speciosa	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10533	Ixeris chinensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO25675	Anthyllis onobrychoides	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO317	Corticium simplex	Species	Plakinidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8453	Euphorbia pannonica	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6163	Picris conyzoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2677	Paralemnalia clavata	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8554	Cryptocarya lividula	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1996	Penstemon gentianoides	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1569	Mitragyna speciosa	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10533	Ixeris chinensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4209	Knautia montana	Species	Caprifoliaceae	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
ED50	1
Ki	2
Others	26

Activity Type	# Activity
Individual Protein	21
Organism	2
Others	7

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT271	Individual Protein	Delta opioid receptor	Homo sapiens	Inhibition	=	0.6	%	PMID[571448]
NPT223	Individual Protein	Alpha-2b adrenergic receptor	Homo sapiens	Inhibition	=	0.0	%	PMID[571448]
NPT222	Individual Protein	Alpha-2a adrenergic receptor	Homo sapiens	Inhibition	=	7.0	%	PMID[571448]
NPT221	Individual Protein	Alpha-1d adrenergic receptor	Homo sapiens	Inhibition	=	6.3	%	PMID[571448]
NPT1789	Individual Protein	Alpha-1b adrenergic receptor	Homo sapiens	Inhibition	=	25.2	%	PMID[571448]
NPT1788	Individual Protein	Alpha-1a adrenergic receptor	Homo sapiens	Inhibition	=	16.8	%	PMID[571448]
NPT272	Individual Protein	Kappa opioid receptor	Homo sapiens	Inhibition	=	61.9	%	PMID[571448]
NPT145	Individual Protein	Mu opioid receptor	Homo sapiens	Inhibition	=	64.7	%	PMID[571448]
NPT5971	Individual Protein	Nociceptin receptor	Homo sapiens	Inhibition	=	-14.9	%	PMID[571448]
NPT1788	Individual Protein	Alpha-1a adrenergic receptor	Homo sapiens	Inhibition	=	81.1	%	PMID[571448]
NPT1789	Individual Protein	Alpha-1b adrenergic receptor	Homo sapiens	Inhibition	=	95.6	%	PMID[571448]
NPT221	Individual Protein	Alpha-1d adrenergic receptor	Homo sapiens	Inhibition	=	70.5	%	PMID[571448]
NPT222	Individual Protein	Alpha-2a adrenergic receptor	Homo sapiens	Inhibition	=	73.1	%	PMID[571448]
NPT223	Individual Protein	Alpha-2b adrenergic receptor	Homo sapiens	Inhibition	=	67.2	%	PMID[571448]
NPT271	Individual Protein	Delta opioid receptor	Homo sapiens	Inhibition	=	69.2	%	PMID[571448]
NPT272	Individual Protein	Kappa opioid receptor	Homo sapiens	Inhibition	=	98.5	%	PMID[571448]
NPT145	Individual Protein	Mu opioid receptor	Homo sapiens	Inhibition	=	98.0	%	PMID[571448]
NPT5971	Individual Protein	Nociceptin receptor	Homo sapiens	Inhibition	=	31.8	%	PMID[571448]
NPT272	Individual Protein	Kappa opioid receptor	Homo sapiens	Ki	=	116.0	nM	PMID[571448]
NPT145	Individual Protein	Mu opioid receptor	Homo sapiens	Ki	=	54.5	nM	PMID[571448]
NPT145	Individual Protein	Mu opioid receptor	Homo sapiens	EC50	=	39.2	nM	PMID[571448]
NPT27	Others	Unspecified		ERH	=	0.03	n.a.	PMID[571448]
NPT27	Others	Unspecified		CL	=	0.5	mL.min-1.kg-1	PMID[571448]
NPT27	Others	Unspecified		CL	=	14.9	mL.min-1.kg-1	PMID[571448]
NPT27	Others	Unspecified		Fu	=	0.276	n.a.	PMID[571448]
NPT27	Others	Unspecified		Fu	=	0.01	n.a.	PMID[571448]
NPT27	Others	Unspecified		T1/2	=	0.6967	hr	PMID[571448]
NPT27	Others	Unspecified		Kel	=	0.0166	/min	PMID[571448]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	ED50	=	6.25	mg.kg-1	PMID[571448]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	MPE	=	100.0	%	PMID[571448]

☑ 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 NPC100898 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	341
0.1-0.2	2171
0.2-0.3	11192
0.3-0.4	6609
0.4-0.5	15840
0.5-0.6	3445
0.6-0.7	2292
0.7-0.8	706
0.8-0.85	76
0.85-0.9	21
0.9-0.95	1
0.95-1	3

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 NPC100898 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	203
0.1-0.2	574
0.2-0.3	798
0.3-0.4	1130
0.4-0.5	2392
0.5-0.6	2597
0.6-0.7	1239
0.7-0.8	203
0.8-0.85	13
0.85-0.9	1
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