NPASS Compound

Structure

NPC96272 OpenBabel07101719512D 21 21 0 0 0 0 0 0 0 0999 V2000 -8.0926 -5.2450 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1537 -1.1999 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0981 -5.3495 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5103 -4.5405 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1646 -1.4090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1701 -1.5135 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 -3.7524 -2.2180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9170 -3.6270 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5823 -0.7045 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 1.5388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3347 -2.9225 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7469 -2.1135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3292 -2.8180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5878 -0.8090 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 -6.7360 -1.9044 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1810 -1.7226 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2601 1.2601 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 3 1 0 0 0 0 2 14 1 0 0 0 0 3 4 1 0 0 0 0 4 9 1 0 0 0 0 5 6 1 0 0 0 0 5 8 2 0 0 0 0 6 10 1 0 0 0 0 7 11 1 0 0 0 0 7 12 1 0 0 0 0 8 14 1 0 0 0 0 9 15 1 0 0 0 0 10 16 1 0 0 0 0 11 17 1 0 0 0 0 12 18 1 0 0 0 0 13 14 2 0 0 0 0 13 15 1 0 0 0 0 15 19 2 0 0 0 0 16 18 1 0 0 0 0 16 20 2 0 0 0 0 17 18 1 0 0 0 0 17 21 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	291.18
Volume:	318.217
LogP:	2.915
LogD:	1.913
LogS:	-2.645
# Rotatable Bonds:	9
TPSA:	54.45
# H-Bond Aceptor:	4
# H-Bond Donor:	0
# Rings:	1
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.51
Synthetic Accessibility Score:	2.79
Fsp3:	0.588
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:	-4.711
MDCK Permeability:	2.7429303372628056e-05
Pgp-inhibitor:	0.937
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.015
20% Bioavailability (F20%):	0.948
30% Bioavailability (F30%):	0.948

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.996
Plasma Protein Binding (PPB):	85.19808959960938%
Volume Distribution (VD):	0.516
Pgp-substrate:	24.92279624938965%

ADMET: Metabolism

CYP1A2-inhibitor:	0.212
CYP1A2-substrate:	0.918
CYP2C19-inhibitor:	0.54
CYP2C19-substrate:	0.767
CYP2C9-inhibitor:	0.598
CYP2C9-substrate:	0.754
CYP2D6-inhibitor:	0.093
CYP2D6-substrate:	0.189
CYP3A4-inhibitor:	0.63
CYP3A4-substrate:	0.462

ADMET: Excretion

Clearance (CL):	7.113
Half-life (T1/2):	0.878

ADMET: Toxicity

hERG Blockers:	0.024
Human Hepatotoxicity (H-HT):	0.435
Drug-inuced Liver Injury (DILI):	0.051
AMES Toxicity:	0.022
Rat Oral Acute Toxicity:	0.091
Maximum Recommended Daily Dose:	0.789
Skin Sensitization:	0.966
Carcinogencity:	0.765
Eye Corrosion:	0.003
Eye Irritation:	0.038
Respiratory Toxicity:	0.115

Download Data

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

Natural Product: NPC96272

Natural Product ID:	NPC96272
*Common Name:**	Formosusin B
IUPAC Name:	(4E,6E)-6-methyl-1-(2-oxopyrrolidin-1-yl)dodeca-4,6-diene-1,8-dione
Synonyms:
Standard InCHIKey:	SHWIXYZQCHEFEH-SEYMNPNRSA-N
Standard InCHI:	InChI=1S/C17H25NO3/c1-3-4-9-15(19)13-14(2)8-5-6-10-16(20)18-12-7-11-17(18)21/h5,8,13H,3-4,6-7,9-12H2,1-2H3/b8-5+,14-13+
SMILES:	CCCCC(=O)/C=C(C)/C=C/CCC(=O)N1CCCC1=O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL3127728
PubChem CID:	76318301
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000218] Pyrrolidines [CHEMONTID:0003023] N-acylpyrrolidines

*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
NPO32913	paecilomyces formosus	Species	Thermoascaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24411199]

☑ 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	26

Activity Type	# Activity
Individual Protein	16
Others	10

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT6348	Individual Protein	DNA polymerase lambda	Mus musculus	IC50	>	200000.0	nM	PMID[514210]
NPT4478	Individual Protein	Deoxyribonuclease-1	Bos taurus	IC50	>	200000.0	nM	PMID[514210]
NPT6223	Individual Protein	Polynucleotide kinase	Enterobacteria phage T4	IC50	>	200000.0	nM	PMID[514210]
NPT6383	Individual Protein	Inosine-5'-monophosphate dehydrogenase 2	Mus musculus	IC50	>	200000.0	nM	PMID[514210]
NPT6594	Individual Protein	DNA-directed RNA polymerase	Enterobacteria phage T7	IC50	>	200000.0	nM	PMID[514210]
NPT459	Individual Protein	Human immunodeficiency virus type 1 reverse transcriptase	Human immunodeficiency virus 1	IC50	>	200000.0	nM	PMID[514210]
NPT6333	Individual Protein	DNA polymerase	Enterobacteria phage T4	IC50	>	200000.0	nM	PMID[514210]
NPT6320	Individual Protein	DNA polymerase delta catalytic subunit	Drosophila melanogaster	IC50	>	200000.0	nM	PMID[514210]
NPT6429	Individual Protein	DNA polymerase alpha catalytic subunit	Drosophila melanogaster	IC50	>	200000.0	nM	PMID[514210]
NPT199	Individual Protein	DNA polymerase kappa	Homo sapiens	IC50	>	200000.0	nM	PMID[514210]
NPT4538	Individual Protein	DNA nucleotidylexotransferase	Bos taurus	IC50	>	200000.0	nM	PMID[514210]
NPT4232	Individual Protein	DNA polymerase delta subunit 1	Homo sapiens	IC50	>	200000.0	nM	PMID[514210]
NPT2216	Individual Protein	DNA polymerase beta	Rattus norvegicus	IC50	>	200000.0	nM	PMID[514210]
NPT3732	Individual Protein	DNA polymerase lambda	Homo sapiens	IC50	>	200000.0	nM	PMID[514210]
NPT6396	Individual Protein	DNA-directed DNA/RNA polymerase mu	Homo sapiens	IC50	>	200000.0	nM	PMID[514210]
NPT2	Others	Unspecified		IC50	>	200000.0	nM	PMID[514210]
NPT9	Individual Protein	DNA polymerase eta	Homo sapiens	IC50	>	200000.0	nM	PMID[514210]

☑ 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 NPC96272 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	58
0.1-0.2	3572
0.2-0.3	25871
0.3-0.4	10513
0.4-0.5	2424
0.5-0.6	235
0.6-0.7	17
0.7-0.8	5
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.8154	Intermediate Similarity	NPC133923
0.8	Intermediate Similarity	NPC385
0.7922	Intermediate Similarity	NPC277341
0.7922	Intermediate Similarity	NPC226982
0.791	Intermediate Similarity	NPC252684
0.7662	Intermediate Similarity	NPC471768
0.7246	Intermediate Similarity	NPC42477
0.6962	Remote Similarity	NPC46268
0.6944	Remote Similarity	NPC206660
0.6786	Remote Similarity	NPC475975
0.6548	Remote Similarity	NPC473810
0.6512	Remote Similarity	NPC319913
0.6463	Remote Similarity	NPC28529
0.6437	Remote Similarity	NPC322672
0.6364	Remote Similarity	NPC324506
0.6364	Remote Similarity	NPC473525
0.6322	Remote Similarity	NPC76283
0.6282	Remote Similarity	NPC90782
0.625	Remote Similarity	NPC469861
0.625	Remote Similarity	NPC469860
0.625	Remote Similarity	NPC130436
0.625	Remote Similarity	NPC252503
0.6203	Remote Similarity	NPC97614
0.6203	Remote Similarity	NPC328895
0.6154	Remote Similarity	NPC53240
0.6098	Remote Similarity	NPC34672
0.6081	Remote Similarity	NPC6795
0.6076	Remote Similarity	NPC477688
0.6061	Remote Similarity	NPC100380
0.6029	Remote Similarity	NPC15325
0.6	Remote Similarity	NPC45283
0.593	Remote Similarity	NPC209232
0.5909	Remote Similarity	NPC191337
0.5897	Remote Similarity	NPC187315
0.587	Remote Similarity	NPC81195
0.5833	Remote Similarity	NPC320667
0.5833	Remote Similarity	NPC214125
0.5821	Remote Similarity	NPC262558
0.5821	Remote Similarity	NPC8610
0.5821	Remote Similarity	NPC471752
0.5816	Remote Similarity	NPC474985
0.5816	Remote Similarity	NPC26597
0.5806	Remote Similarity	NPC47230
0.5806	Remote Similarity	NPC17143
0.58	Remote Similarity	NPC474828
0.58	Remote Similarity	NPC68001
0.58	Remote Similarity	NPC199831
0.58	Remote Similarity	NPC474827
0.5789	Remote Similarity	NPC313265
0.5789	Remote Similarity	NPC474974
0.5775	Remote Similarity	NPC37644
0.5773	Remote Similarity	NPC52820
0.5765	Remote Similarity	NPC25513
0.5758	Remote Similarity	NPC477686
0.5714	Remote Similarity	NPC322457
0.5714	Remote Similarity	NPC63284
0.5694	Remote Similarity	NPC322461
0.5663	Remote Similarity	NPC326126
0.5652	Remote Similarity	NPC145311
0.5638	Remote Similarity	NPC473056
0.5606	Remote Similarity	NPC301972
0.5604	Remote Similarity	NPC296589
0.5604	Remote Similarity	NPC475614

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 NPC96272 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	70
0.1-0.2	922
0.2-0.3	5492
0.3-0.4	2266
0.4-0.5	379
0.5-0.6	21
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
0.5904	Remote Similarity	NPD1452	Discontinued
0.5714	Remote Similarity	NPD466	Approved
0.5676	Remote Similarity	NPD605	Clinical (unspecified phase)
0.5657	Remote Similarity	NPD742	Approved
0.5625	Remote Similarity	NPD3709	Clinical (unspecified phase)

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