NPASS Compound

Structure

NPC473810 OpenBabel07101718222D 24 24 0 0 1 0 0 0 0 0999 V2000 10.9839 -6.9006 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.2096 -4.2644 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9511 0.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.3906 -5.9870 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6437 -3.8735 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0559 -3.0645 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6382 -3.7690 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0614 -3.1691 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2260 -4.5780 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4736 -2.3600 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2206 -4.4735 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4791 -2.4646 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.8083 -5.2825 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8913 -1.6555 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8090 0.5878 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.8029 -5.1780 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 1.8968 -1.7601 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6180 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3090 -0.9511 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3090 -0.9511 0.0000 C 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 1.4901 -2.6736 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5691 0.3090 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2788 -1.7601 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 4 1 0 0 0 0 2 16 1 0 0 0 0 3 21 1 0 0 0 0 4 16 1 0 0 0 0 5 6 1 0 0 0 0 5 7 1 0 0 0 0 6 8 1 0 0 0 0 7 9 1 0 0 0 0 8 10 1 0 0 0 0 9 11 1 0 0 0 0 10 12 1 0 0 0 0 11 13 1 0 0 0 0 12 14 1 0 0 0 0 13 16 1 0 0 0 0 14 17 1 0 0 0 0 15 18 1 0 0 0 0 15 21 1 0 0 0 0 17 19 2 0 0 0 0 17 22 1 0 0 0 0 18 19 1 0 0 0 0 18 23 2 0 0 0 0 19 20 1 0 0 0 0 20 21 1 0 0 0 0 20 24 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	337.26
Volume:	375.378
LogP:	6.735
LogD:	4.707
LogS:	-3.072
# Rotatable Bonds:	13
TPSA:	62.46
# H-Bond Aceptor:	4
# H-Bond Donor:	2
# Rings:	1
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.365
Synthetic Accessibility Score:	3.122
Fsp3:	0.75
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.702
MDCK Permeability:	1.8074319086736068e-05
Pgp-inhibitor:	0.178
Pgp-substrate:	0.003
Human Intestinal Absorption (HIA):	0.015
20% Bioavailability (F20%):	0.998
30% Bioavailability (F30%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.781
Plasma Protein Binding (PPB):	97.52182006835938%
Volume Distribution (VD):	0.977
Pgp-substrate:	1.5642884969711304%

ADMET: Metabolism

CYP1A2-inhibitor:	0.872
CYP1A2-substrate:	0.226
CYP2C19-inhibitor:	0.735
CYP2C19-substrate:	0.212
CYP2C9-inhibitor:	0.414
CYP2C9-substrate:	0.938
CYP2D6-inhibitor:	0.75
CYP2D6-substrate:	0.116
CYP3A4-inhibitor:	0.295
CYP3A4-substrate:	0.076

ADMET: Excretion

Clearance (CL):	4.523
Half-life (T1/2):	0.12

ADMET: Toxicity

hERG Blockers:	0.016
Human Hepatotoxicity (H-HT):	0.164
Drug-inuced Liver Injury (DILI):	0.378
AMES Toxicity:	0.225
Rat Oral Acute Toxicity:	0.284
Maximum Recommended Daily Dose:	0.079
Skin Sensitization:	0.828
Carcinogencity:	0.268
Eye Corrosion:	0.009
Eye Irritation:	0.731
Respiratory Toxicity:	0.785

Download Data

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

Natural Product: NPC473810

Natural Product ID:	NPC473810
*Common Name:**	Melophlin I
IUPAC Name:	(3Z)-3-(1-hydroxy-12-methyltetradecylidene)-1-methylpyrrolidine-2,4-dione
Synonyms:	Melophlin I
Standard InCHIKey:	RHBKMLLQJHQQDJ-ZPHPHTNESA-N
Standard InCHI:	InChI=1S/C20H35NO3/c1-4-16(2)13-11-9-7-5-6-8-10-12-14-17(22)19-18(23)15-21(3)20(19)24/h16,22H,4-15H2,1-3H3/b19-17-
SMILES:	CCC(C)CCCCCCCCCCC(=C1C(=O)CN(C1=O)C)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL452493
PubChem CID:	54704116
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000218] Pyrrolidines [CHEMONTID:0003449] N-alkylpyrrolidines

*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
NPO16110	Melophlus sarassinorum	Species	Ancorinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[12542345]
NPO16110	Melophlus sarassinorum	Species	Ancorinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[16124767]
NPO16110	Melophlus sarassinorum	Species	Ancorinidae	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
IC50	1

Activity Type	# Activity
Organism	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT176	Organism	Artemia salina	Artemia salina	IC50	=	52.6	ug.mL-1	PMID[456290]

☑ 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 NPC473810 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	69
0.1-0.2	745
0.2-0.3	18530
0.3-0.4	15962
0.4-0.5	6830
0.5-0.6	515
0.6-0.7	37
0.7-0.8	4
0.8-0.85	0
0.85-0.9	0
0.9-0.95	4
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.95	High Similarity	NPC322672
0.9383	High Similarity	NPC473525
0.9375	High Similarity	NPC319913
0.9342	High Similarity	NPC46268
0.7391	Intermediate Similarity	NPC47230
0.7391	Intermediate Similarity	NPC17143
0.6882	Remote Similarity	NPC324506
0.6593	Remote Similarity	NPC277341
0.6593	Remote Similarity	NPC226982
0.6569	Remote Similarity	NPC77703
0.6548	Remote Similarity	NPC96272
0.6538	Remote Similarity	NPC469604
0.6471	Remote Similarity	NPC316730
0.6389	Remote Similarity	NPC469603
0.6355	Remote Similarity	NPC470072
0.6355	Remote Similarity	NPC476276
0.633	Remote Similarity	NPC474411
0.633	Remote Similarity	NPC474431
0.6321	Remote Similarity	NPC476328
0.6316	Remote Similarity	NPC76283
0.6226	Remote Similarity	NPC470073
0.6216	Remote Similarity	NPC469597
0.6204	Remote Similarity	NPC207820
0.6186	Remote Similarity	NPC309525
0.6154	Remote Similarity	NPC477964
0.6132	Remote Similarity	NPC318544
0.6111	Remote Similarity	NPC176773
0.6111	Remote Similarity	NPC34672
0.6095	Remote Similarity	NPC188785
0.6078	Remote Similarity	NPC150041
0.6038	Remote Similarity	NPC474244
0.6024	Remote Similarity	NPC252684
0.6	Remote Similarity	NPC53240
0.6	Remote Similarity	NPC61473
0.6	Remote Similarity	NPC474006
0.6	Remote Similarity	NPC26597
0.5981	Remote Similarity	NPC476877
0.5962	Remote Similarity	NPC52820
0.5962	Remote Similarity	NPC476344
0.596	Remote Similarity	NPC322966
0.5957	Remote Similarity	NPC209232
0.5955	Remote Similarity	NPC469836
0.5926	Remote Similarity	NPC192843
0.5926	Remote Similarity	NPC476921
0.5909	Remote Similarity	NPC474099
0.5909	Remote Similarity	NPC477688
0.5909	Remote Similarity	NPC90782
0.59	Remote Similarity	NPC81195
0.5882	Remote Similarity	NPC38172
0.5876	Remote Similarity	NPC475975
0.5872	Remote Similarity	NPC476876
0.5851	Remote Similarity	NPC471768
0.5843	Remote Similarity	NPC328895
0.5842	Remote Similarity	NPC159568
0.5833	Remote Similarity	NPC199831
0.5833	Remote Similarity	NPC474828
0.5833	Remote Similarity	NPC474827
0.5833	Remote Similarity	NPC68001
0.5824	Remote Similarity	NPC469835
0.5814	Remote Similarity	NPC474304
0.5814	Remote Similarity	NPC474329
0.5806	Remote Similarity	NPC120335
0.5794	Remote Similarity	NPC474001
0.5784	Remote Similarity	NPC145707
0.5783	Remote Similarity	NPC133923
0.578	Remote Similarity	NPC87919
0.578	Remote Similarity	NPC133420
0.5752	Remote Similarity	NPC58281
0.5745	Remote Similarity	NPC469492
0.5732	Remote Similarity	NPC281230
0.573	Remote Similarity	NPC67608
0.573	Remote Similarity	NPC469914
0.5727	Remote Similarity	NPC476926
0.5726	Remote Similarity	NPC471109
0.5702	Remote Similarity	NPC314550
0.5701	Remote Similarity	NPC233932
0.5701	Remote Similarity	NPC474985
0.5684	Remote Similarity	NPC469517
0.5682	Remote Similarity	NPC476626
0.5676	Remote Similarity	NPC271562
0.567	Remote Similarity	NPC469838
0.567	Remote Similarity	NPC469833
0.5667	Remote Similarity	NPC97614
0.5663	Remote Similarity	NPC385
0.566	Remote Similarity	NPC91036
0.5644	Remote Similarity	NPC116231
0.5636	Remote Similarity	NPC470596
0.5625	Remote Similarity	NPC171734
0.5625	Remote Similarity	NPC476918
0.5619	Remote Similarity	NPC471635
0.5619	Remote Similarity	NPC25033
0.5619	Remote Similarity	NPC119225
0.5619	Remote Similarity	NPC470382
0.5619	Remote Similarity	NPC476261
0.5618	Remote Similarity	NPC476614
0.5614	Remote Similarity	NPC476875
0.56	Remote Similarity	NPC157479
0.56	Remote Similarity	NPC472136

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 NPC473810 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	73
0.1-0.2	717
0.2-0.3	4437
0.3-0.4	3090
0.4-0.5	789
0.5-0.6	44
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
0.6	Remote Similarity	NPD7341	Phase 2
0.5929	Remote Similarity	NPD1376	Discontinued
0.5816	Remote Similarity	NPD3723	Clinical (unspecified phase)
0.5747	Remote Similarity	NPD7331	Phase 2
0.5727	Remote Similarity	NPD7333	Discontinued

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