NPASS Compound

Structure

NPC277341 OpenBabel07101719512D 21 21 0 0 1 0 0 0 0 0999 V2000 -9.0947 -1.1339 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3395 0.4112 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3516 -1.8030 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4005 -1.4940 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8532 -0.9271 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1100 -1.5962 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 -3.8042 -1.2361 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1926 -0.5158 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1590 -1.2872 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 0.3090 0.9511 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4984 -0.8760 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5474 -0.5669 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2416 -0.2068 0.0000 C 0 0 2 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 0.8090 -0.5878 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 -6.0337 0.7713 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6942 0.3601 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8090 -1.5878 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 2 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 1 1 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:	2.434
LogD:	1.468
LogS:	-3.694
# Rotatable Bonds:	8
TPSA:	57.61
# H-Bond Aceptor:	4
# H-Bond Donor:	1
# Rings:	1
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.579
Synthetic Accessibility Score:	3.436
Fsp3:	0.529
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.612
MDCK Permeability:	2.376657175773289e-05
Pgp-inhibitor:	0.566
Pgp-substrate:	0.039
Human Intestinal Absorption (HIA):	0.388
20% Bioavailability (F20%):	0.859
30% Bioavailability (F30%):	0.312

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.938
Plasma Protein Binding (PPB):	74.22179412841797%
Volume Distribution (VD):	0.569
Pgp-substrate:	31.41996192932129%

ADMET: Metabolism

CYP1A2-inhibitor:	0.841
CYP1A2-substrate:	0.836
CYP2C19-inhibitor:	0.71
CYP2C19-substrate:	0.82
CYP2C9-inhibitor:	0.578
CYP2C9-substrate:	0.818
CYP2D6-inhibitor:	0.484
CYP2D6-substrate:	0.191
CYP3A4-inhibitor:	0.504
CYP3A4-substrate:	0.374

ADMET: Excretion

Clearance (CL):	7.384
Half-life (T1/2):	0.655

ADMET: Toxicity

hERG Blockers:	0.098
Human Hepatotoxicity (H-HT):	0.563
Drug-inuced Liver Injury (DILI):	0.134
AMES Toxicity:	0.012
Rat Oral Acute Toxicity:	0.107
Maximum Recommended Daily Dose:	0.954
Skin Sensitization:	0.895
Carcinogencity:	0.394
Eye Corrosion:	0.018
Eye Irritation:	0.335
Respiratory Toxicity:	0.583

Download Data

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

Natural Product: NPC277341

Natural Product ID:	NPC277341
*Common Name:**	Formosusin A
IUPAC Name:	1-[(2Z,4E,6E,8R)-8-hydroxy-6-methyldodeca-2,4,6-trienoyl]pyrrolidin-2-one
Synonyms:
Standard InCHIKey:	ZYPGADGCNXOUJP-FMHFZIMOSA-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/h5-6,8,10,13,15,19H,3-4,7,9,11-12H2,1-2H3/b8-5+,10-6-,14-13+/t15-/m1/s1
SMILES:	CCCC[C@H](/C=C(C)/C=C/C=CC(=O)N1CCCC1=O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL3127730
PubChem CID:	76332847
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
Ki	2

Activity Type	# Activity
Individual Protein	18
Others	10

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2216	Individual Protein	DNA polymerase beta	Rattus norvegicus	Ki	=	11600.0	nM	PMID[511096]
NPT2216	Individual Protein	DNA polymerase beta	Rattus norvegicus	Ki	=	5500.0	nM	PMID[511096]
NPT6348	Individual Protein	DNA polymerase lambda	Mus musculus	IC50	>	200000.0	nM	PMID[511096]
NPT4478	Individual Protein	Deoxyribonuclease-1	Bos taurus	IC50	>	200000.0	nM	PMID[511096]
NPT6223	Individual Protein	Polynucleotide kinase	Enterobacteria phage T4	IC50	>	200000.0	nM	PMID[511096]
NPT6383	Individual Protein	Inosine-5'-monophosphate dehydrogenase 2	Mus musculus	IC50	>	200000.0	nM	PMID[511096]
NPT6594	Individual Protein	DNA-directed RNA polymerase	Enterobacteria phage T7	IC50	>	200000.0	nM	PMID[511096]
NPT459	Individual Protein	Human immunodeficiency virus type 1 reverse transcriptase	Human immunodeficiency virus 1	IC50	>	200000.0	nM	PMID[511096]
NPT6333	Individual Protein	DNA polymerase	Enterobacteria phage T4	IC50	>	200000.0	nM	PMID[511096]
NPT6320	Individual Protein	DNA polymerase delta catalytic subunit	Drosophila melanogaster	IC50	>	200000.0	nM	PMID[511096]
NPT6429	Individual Protein	DNA polymerase alpha catalytic subunit	Drosophila melanogaster	IC50	>	200000.0	nM	PMID[511096]
NPT199	Individual Protein	DNA polymerase kappa	Homo sapiens	IC50	>	200000.0	nM	PMID[511096]
NPT4538	Individual Protein	DNA nucleotidylexotransferase	Bos taurus	IC50	>	200000.0	nM	PMID[511096]
NPT4232	Individual Protein	DNA polymerase delta subunit 1	Homo sapiens	IC50	>	200000.0	nM	PMID[511096]
NPT2216	Individual Protein	DNA polymerase beta	Rattus norvegicus	IC50	=	35600.0	nM	PMID[511096]
NPT3732	Individual Protein	DNA polymerase lambda	Homo sapiens	IC50	>	200000.0	nM	PMID[511096]
NPT6396	Individual Protein	DNA-directed DNA/RNA polymerase mu	Homo sapiens	IC50	>	200000.0	nM	PMID[511096]
NPT2	Others	Unspecified		IC50	>	200000.0	nM	PMID[511096]
NPT9	Individual Protein	DNA polymerase eta	Homo sapiens	IC50	>	200000.0	nM	PMID[511096]

☑ 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 NPC277341 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	61
0.1-0.2	459
0.2-0.3	17145
0.3-0.4	17571
0.4-0.5	6371
0.5-0.6	1028
0.6-0.7	54
0.7-0.8	5
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC226982
0.8659	High Similarity	NPC475975
0.8049	Intermediate Similarity	NPC471768
0.7922	Intermediate Similarity	NPC96272
0.7333	Intermediate Similarity	NPC133923
0.72	Intermediate Similarity	NPC385
0.7143	Intermediate Similarity	NPC34672
0.7143	Intermediate Similarity	NPC252684
0.7126	Intermediate Similarity	NPC209232
0.6977	Remote Similarity	NPC46268
0.6837	Remote Similarity	NPC52820
0.6832	Remote Similarity	NPC474828
0.6832	Remote Similarity	NPC474827
0.6832	Remote Similarity	NPC68001
0.6832	Remote Similarity	NPC199831
0.6706	Remote Similarity	NPC326126
0.6634	Remote Similarity	NPC77703
0.6596	Remote Similarity	NPC324506
0.6593	Remote Similarity	NPC473810
0.6582	Remote Similarity	NPC42477
0.6571	Remote Similarity	NPC474099
0.6569	Remote Similarity	NPC474244
0.6548	Remote Similarity	NPC471022
0.6535	Remote Similarity	NPC316730
0.6531	Remote Similarity	NPC313265
0.6481	Remote Similarity	NPC314550
0.6471	Remote Similarity	NPC97614
0.6471	Remote Similarity	NPC188785
0.6458	Remote Similarity	NPC81195
0.6392	Remote Similarity	NPC53240
0.6383	Remote Similarity	NPC319913
0.6353	Remote Similarity	NPC90782
0.6353	Remote Similarity	NPC236208
0.6346	Remote Similarity	NPC318544
0.6341	Remote Similarity	NPC206660
0.6339	Remote Similarity	NPC470300
0.6316	Remote Similarity	NPC130436
0.6316	Remote Similarity	NPC469860
0.6316	Remote Similarity	NPC469861
0.6316	Remote Similarity	NPC322672
0.6293	Remote Similarity	NPC36254
0.6286	Remote Similarity	NPC470073
0.6282	Remote Similarity	NPC472808
0.6282	Remote Similarity	NPC324224
0.6262	Remote Similarity	NPC470072
0.625	Remote Similarity	NPC473525
0.6235	Remote Similarity	NPC23721
0.6214	Remote Similarity	NPC474985
0.6203	Remote Similarity	NPC268185
0.6176	Remote Similarity	NPC476344
0.6139	Remote Similarity	NPC469739
0.6139	Remote Similarity	NPC150041
0.6136	Remote Similarity	NPC252503
0.6118	Remote Similarity	NPC106613
0.6104	Remote Similarity	NPC217188
0.6071	Remote Similarity	NPC272166
0.6067	Remote Similarity	NPC470992
0.6067	Remote Similarity	NPC470993
0.6067	Remote Similarity	NPC227396
0.6061	Remote Similarity	NPC17143
0.6061	Remote Similarity	NPC47230
0.6058	Remote Similarity	NPC233932
0.6058	Remote Similarity	NPC26597
0.6053	Remote Similarity	NPC476155
0.6053	Remote Similarity	NPC17581
0.6024	Remote Similarity	NPC471023
0.6019	Remote Similarity	NPC471447
0.6018	Remote Similarity	NPC66007
0.6	Remote Similarity	NPC144714
0.6	Remote Similarity	NPC470788
0.6	Remote Similarity	NPC100810
0.6	Remote Similarity	NPC469603
0.6	Remote Similarity	NPC71755
0.5981	Remote Similarity	NPC469604
0.5977	Remote Similarity	NPC143396
0.5977	Remote Similarity	NPC477688
0.5976	Remote Similarity	NPC327112
0.5976	Remote Similarity	NPC6795
0.5963	Remote Similarity	NPC207820
0.5955	Remote Similarity	NPC314678
0.5949	Remote Similarity	NPC317899
0.5922	Remote Similarity	NPC175614
0.5921	Remote Similarity	NPC225974
0.5909	Remote Similarity	NPC133700
0.5888	Remote Similarity	NPC476877
0.5882	Remote Similarity	NPC97580
0.5882	Remote Similarity	NPC474974
0.5862	Remote Similarity	NPC474823
0.5862	Remote Similarity	NPC309466
0.5854	Remote Similarity	NPC322002
0.5854	Remote Similarity	NPC318306
0.5843	Remote Similarity	NPC67076
0.5843	Remote Similarity	NPC95863
0.5843	Remote Similarity	NPC316185
0.5843	Remote Similarity	NPC319163
0.5833	Remote Similarity	NPC473737
0.5823	Remote Similarity	NPC189677
0.5823	Remote Similarity	NPC300121
0.5818	Remote Similarity	NPC476276
0.5814	Remote Similarity	NPC146811
0.5814	Remote Similarity	NPC129995
0.5814	Remote Similarity	NPC315141
0.5804	Remote Similarity	NPC168758
0.5804	Remote Similarity	NPC58281
0.5804	Remote Similarity	NPC47857
0.5804	Remote Similarity	NPC181510
0.5795	Remote Similarity	NPC475004
0.5794	Remote Similarity	NPC473289
0.5789	Remote Similarity	NPC267110
0.5789	Remote Similarity	NPC474984
0.5783	Remote Similarity	NPC305973
0.578	Remote Similarity	NPC472856
0.578	Remote Similarity	NPC476876
0.5778	Remote Similarity	NPC284006
0.5778	Remote Similarity	NPC238948
0.5778	Remote Similarity	NPC12815
0.5778	Remote Similarity	NPC26932
0.5778	Remote Similarity	NPC215745
0.5747	Remote Similarity	NPC98329
0.5747	Remote Similarity	NPC7392
0.5741	Remote Similarity	NPC6271
0.5714	Remote Similarity	NPC474545
0.5714	Remote Similarity	NPC315843
0.5714	Remote Similarity	NPC288381
0.5714	Remote Similarity	NPC470994
0.5714	Remote Similarity	NPC269737
0.5714	Remote Similarity	NPC241426
0.5714	Remote Similarity	NPC20934
0.5714	Remote Similarity	NPC26810
0.5714	Remote Similarity	NPC91036
0.57	Remote Similarity	NPC155230
0.5698	Remote Similarity	NPC245947
0.5698	Remote Similarity	NPC136164
0.5698	Remote Similarity	NPC323045
0.5698	Remote Similarity	NPC255863
0.5698	Remote Similarity	NPC477525
0.5698	Remote Similarity	NPC317881
0.5696	Remote Similarity	NPC61177
0.5688	Remote Similarity	NPC64168
0.5688	Remote Similarity	NPC133420
0.5684	Remote Similarity	NPC476560
0.5667	Remote Similarity	NPC293114
0.5663	Remote Similarity	NPC322186
0.5663	Remote Similarity	NPC329249
0.5657	Remote Similarity	NPC202056
0.5656	Remote Similarity	NPC262880
0.5656	Remote Similarity	NPC247902
0.5652	Remote Similarity	NPC478196
0.5652	Remote Similarity	NPC103391
0.5652	Remote Similarity	NPC478191
0.5652	Remote Similarity	NPC478192
0.5652	Remote Similarity	NPC161038
0.5652	Remote Similarity	NPC472536
0.5652	Remote Similarity	NPC478195
0.5652	Remote Similarity	NPC478193
0.5652	Remote Similarity	NPC260396
0.5652	Remote Similarity	NPC478194
0.5647	Remote Similarity	NPC477106
0.5647	Remote Similarity	NPC322457
0.5647	Remote Similarity	NPC68110
0.5645	Remote Similarity	NPC41162
0.5641	Remote Similarity	NPC474495
0.5641	Remote Similarity	NPC59408
0.5641	Remote Similarity	NPC473672
0.5641	Remote Similarity	NPC71053
0.5638	Remote Similarity	NPC28529
0.5638	Remote Similarity	NPC473471
0.5636	Remote Similarity	NPC471259
0.5636	Remote Similarity	NPC476328
0.5632	Remote Similarity	NPC37382
0.5632	Remote Similarity	NPC187315
0.5631	Remote Similarity	NPC304897
0.5631	Remote Similarity	NPC38172
0.5625	Remote Similarity	NPC21324
0.5625	Remote Similarity	NPC110732
0.5625	Remote Similarity	NPC322461
0.5625	Remote Similarity	NPC184473
0.5615	Remote Similarity	NPC315848
0.5615	Remote Similarity	NPC315210
0.5614	Remote Similarity	NPC474497
0.5614	Remote Similarity	NPC474995
0.5612	Remote Similarity	NPC161670
0.561	Remote Similarity	NPC245650
0.5607	Remote Similarity	NPC477964
0.56	Remote Similarity	NPC120335

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 NPC277341 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	72
0.1-0.2	399
0.2-0.3	4382
0.3-0.4	3529
0.4-0.5	715
0.5-0.6	52
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	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.618	Remote Similarity	NPD1452	Discontinued
0.6075	Remote Similarity	NPD7333	Discontinued
0.6071	Remote Similarity	NPD1000	Clinical (unspecified phase)
0.5976	Remote Similarity	NPD4246	Clinical (unspecified phase)
0.5747	Remote Similarity	NPD9137	Approved
0.5741	Remote Similarity	NPD2905	Discontinued
0.566	Remote Similarity	NPD211	Approved
0.566	Remote Similarity	NPD210	Approved

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