NPASS Compound

Structure

Physi-Chem Properties

Molecular Weight:	236.14
Volume:	257.969
LogP:	2.82
LogD:	2.877
LogS:	-2.754
# Rotatable Bonds:	7
TPSA:	50.44
# H-Bond Aceptor:	3
# H-Bond Donor:	1
# Rings:	1
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.582
Synthetic Accessibility Score:	3.023
Fsp3:	0.5
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:	-4.624
MDCK Permeability:	2.295912054250948e-05
Pgp-inhibitor:	0.001
Pgp-substrate:	0.008
Human Intestinal Absorption (HIA):	0.007
20% Bioavailability (F20%):	0.014
30% Bioavailability (F30%):	0.009

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.467
Plasma Protein Binding (PPB):	97.46714782714844%
Volume Distribution (VD):	1.25
Pgp-substrate:	3.3045809268951416%

ADMET: Metabolism

CYP1A2-inhibitor:	0.388
CYP1A2-substrate:	0.724
CYP2C19-inhibitor:	0.2
CYP2C19-substrate:	0.063
CYP2C9-inhibitor:	0.346
CYP2C9-substrate:	0.913
CYP2D6-inhibitor:	0.126
CYP2D6-substrate:	0.858
CYP3A4-inhibitor:	0.077
CYP3A4-substrate:	0.13

ADMET: Excretion

Clearance (CL):	14.768
Half-life (T1/2):	0.891

ADMET: Toxicity

hERG Blockers:	0.004
Human Hepatotoxicity (H-HT):	0.093
Drug-inuced Liver Injury (DILI):	0.041
AMES Toxicity:	0.005
Rat Oral Acute Toxicity:	0.107
Maximum Recommended Daily Dose:	0.026
Skin Sensitization:	0.671
Carcinogencity:	0.915
Eye Corrosion:	0.462
Eye Irritation:	0.647
Respiratory Toxicity:	0.033

Download Data

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

Natural Product: NPC133904

Natural Product ID:	NPC133904
*Common Name:**	Appenolide A
IUPAC Name:	4-methyl-3-[(E)-8-oxonon-1-enyl]-2H-furan-5-one
Synonyms:
Standard InCHIKey:	LYDASAJHAHFJTL-VQHVLOKHSA-N
Standard InCHI:	InChI=1S/C14H20O3/c1-11(15)8-6-4-3-5-7-9-13-10-17-14(16)12(13)2/h7,9H,3-6,8,10H2,1-2H3/b9-7+
SMILES:	CC(=O)CCCCC/C=C/C1=C(C)C(=O)OC1
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL450558
PubChem CID:	6436279
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001983] Dihydrofurans [CHEMONTID:0001982] Furanones [CHEMONTID:0002223] Butenolides

*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
NPO5352	Podospora appendiculata	Species	Lasiosphaeriaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8482945]
NPO5352	Podospora appendiculata	Species	Lasiosphaeriaceae	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
Others	3

Activity Type	# Activity
Organism	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20	Organism	Candida albicans	Candida albicans	IZ	=	12.0	mm	PMID[482788]
NPT3095	Organism	Sordaria fimicola	Sordaria fimicola	Activity	=	54.0	%	PMID[482788]
NPT6449	Organism	Ascobolus stercorarius	Ascobolus stercorarius	Activity	=	26.0	%	PMID[482788]

☑ 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 NPC133904 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	159
0.1-0.2	2283
0.2-0.3	9896
0.3-0.4	18241
0.4-0.5	7782
0.5-0.6	3221
0.6-0.7	1004
0.7-0.8	101
0.8-0.85	6
0.85-0.9	3
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.873	High Similarity	NPC179087
0.873	High Similarity	NPC210303
0.873	High Similarity	NPC44343
0.85	High Similarity	NPC478117
0.8462	Intermediate Similarity	NPC182794
0.8358	Intermediate Similarity	NPC218477
0.8209	Intermediate Similarity	NPC225272
0.8182	Intermediate Similarity	NPC131174
0.8088	Intermediate Similarity	NPC474823
0.8033	Intermediate Similarity	NPC478120
0.8	Intermediate Similarity	NPC151648
0.7971	Intermediate Similarity	NPC475004
0.7969	Intermediate Similarity	NPC286189
0.7917	Intermediate Similarity	NPC329826
0.7917	Intermediate Similarity	NPC469414
0.7895	Intermediate Similarity	NPC94200
0.7895	Intermediate Similarity	NPC268122
0.7887	Intermediate Similarity	NPC474705
0.7879	Intermediate Similarity	NPC132243
0.7794	Intermediate Similarity	NPC248125
0.7792	Intermediate Similarity	NPC118423
0.7746	Intermediate Similarity	NPC84038
0.7746	Intermediate Similarity	NPC186531
0.7733	Intermediate Similarity	NPC472965
0.7733	Intermediate Similarity	NPC63649
0.7733	Intermediate Similarity	NPC264227
0.7681	Intermediate Similarity	NPC21998
0.7681	Intermediate Similarity	NPC203335
0.7612	Intermediate Similarity	NPC473737
0.76	Intermediate Similarity	NPC299235
0.7571	Intermediate Similarity	NPC470256
0.7568	Intermediate Similarity	NPC27205
0.7532	Intermediate Similarity	NPC42470
0.75	Intermediate Similarity	NPC471299
0.75	Intermediate Similarity	NPC168248
0.7424	Intermediate Similarity	NPC133600
0.7397	Intermediate Similarity	NPC287878
0.7391	Intermediate Similarity	NPC470688
0.7377	Intermediate Similarity	NPC236338
0.7377	Intermediate Similarity	NPC15789
0.7368	Intermediate Similarity	NPC128276
0.7368	Intermediate Similarity	NPC471220
0.7353	Intermediate Similarity	NPC474658
0.7333	Intermediate Similarity	NPC123360
0.7317	Intermediate Similarity	NPC196407
0.7313	Intermediate Similarity	NPC143857
0.7313	Intermediate Similarity	NPC229252
0.7313	Intermediate Similarity	NPC130953
0.7308	Intermediate Similarity	NPC471325
0.7297	Intermediate Similarity	NPC476355
0.7297	Intermediate Similarity	NPC227396
0.7286	Intermediate Similarity	NPC191233
0.7273	Intermediate Similarity	NPC178277
0.726	Intermediate Similarity	NPC163003
0.7237	Intermediate Similarity	NPC65603
0.7237	Intermediate Similarity	NPC57744
0.7237	Intermediate Similarity	NPC41780
0.7237	Intermediate Similarity	NPC187568
0.7231	Intermediate Similarity	NPC245002
0.7231	Intermediate Similarity	NPC221763
0.7222	Intermediate Similarity	NPC470693
0.7222	Intermediate Similarity	NPC236208
0.7215	Intermediate Similarity	NPC173609
0.7213	Intermediate Similarity	NPC135698
0.72	Intermediate Similarity	NPC260396
0.72	Intermediate Similarity	NPC193351
0.72	Intermediate Similarity	NPC226669
0.72	Intermediate Similarity	NPC138408
0.72	Intermediate Similarity	NPC155587
0.7188	Intermediate Similarity	NPC269615
0.7183	Intermediate Similarity	NPC194871
0.7164	Intermediate Similarity	NPC159650
0.7164	Intermediate Similarity	NPC22897
0.7162	Intermediate Similarity	NPC58956
0.7162	Intermediate Similarity	NPC269206
0.7162	Intermediate Similarity	NPC295633
0.7162	Intermediate Similarity	NPC276336
0.7143	Intermediate Similarity	NPC220766
0.7143	Intermediate Similarity	NPC106531
0.7125	Intermediate Similarity	NPC193198
0.7125	Intermediate Similarity	NPC16488
0.7105	Intermediate Similarity	NPC4509
0.7105	Intermediate Similarity	NPC235906
0.7105	Intermediate Similarity	NPC472967
0.7105	Intermediate Similarity	NPC266159
0.7101	Intermediate Similarity	NPC474774
0.7101	Intermediate Similarity	NPC68110
0.7101	Intermediate Similarity	NPC155849
0.7089	Intermediate Similarity	NPC325031
0.7083	Intermediate Similarity	NPC276290
0.7083	Intermediate Similarity	NPC287705
0.7073	Intermediate Similarity	NPC316426
0.7073	Intermediate Similarity	NPC234038
0.7073	Intermediate Similarity	NPC315395
0.7067	Intermediate Similarity	NPC117746
0.7067	Intermediate Similarity	NPC294434
0.7067	Intermediate Similarity	NPC140287
0.7067	Intermediate Similarity	NPC259599
0.7067	Intermediate Similarity	NPC15499
0.7059	Intermediate Similarity	NPC79756
0.7059	Intermediate Similarity	NPC32944
0.7059	Intermediate Similarity	NPC193396
0.7059	Intermediate Similarity	NPC309408
0.7059	Intermediate Similarity	NPC98519
0.7051	Intermediate Similarity	NPC270126
0.7051	Intermediate Similarity	NPC150646
0.7042	Intermediate Similarity	NPC37382
0.7037	Intermediate Similarity	NPC31086
0.7037	Intermediate Similarity	NPC196487
0.7037	Intermediate Similarity	NPC14575
0.7027	Intermediate Similarity	NPC257618
0.7024	Intermediate Similarity	NPC95364
0.7024	Intermediate Similarity	NPC142159
0.7024	Intermediate Similarity	NPC474844
0.7015	Intermediate Similarity	NPC189700
0.7013	Intermediate Similarity	NPC68156
0.7013	Intermediate Similarity	NPC180290
0.7013	Intermediate Similarity	NPC316324
0.7	Intermediate Similarity	NPC35556
0.7	Intermediate Similarity	NPC26600
0.7	Intermediate Similarity	NPC270706
0.7	Intermediate Similarity	NPC471296
0.7	Intermediate Similarity	NPC173409
0.7	Intermediate Similarity	NPC47946
0.7	Intermediate Similarity	NPC34883
0.7	Intermediate Similarity	NPC53136
0.6986	Remote Similarity	NPC232812
0.6986	Remote Similarity	NPC143396
0.6986	Remote Similarity	NPC265574
0.6986	Remote Similarity	NPC476059
0.6986	Remote Similarity	NPC476591
0.6986	Remote Similarity	NPC473603
0.6986	Remote Similarity	NPC88877
0.6977	Remote Similarity	NPC242069
0.6977	Remote Similarity	NPC469939
0.6974	Remote Similarity	NPC478194
0.6974	Remote Similarity	NPC478193
0.6974	Remote Similarity	NPC478192
0.6974	Remote Similarity	NPC478191
0.6974	Remote Similarity	NPC478195
0.6974	Remote Similarity	NPC478196
0.6974	Remote Similarity	NPC228978
0.697	Remote Similarity	NPC150717
0.6962	Remote Similarity	NPC474510
0.6962	Remote Similarity	NPC302426
0.6957	Remote Similarity	NPC217537
0.6951	Remote Similarity	NPC281172
0.6944	Remote Similarity	NPC472266
0.6935	Remote Similarity	NPC145311
0.6933	Remote Similarity	NPC144419
0.6923	Remote Similarity	NPC93763
0.6923	Remote Similarity	NPC267231
0.6923	Remote Similarity	NPC159535
0.6923	Remote Similarity	NPC108816
0.6923	Remote Similarity	NPC151761
0.6923	Remote Similarity	NPC182292
0.6923	Remote Similarity	NPC253749
0.6914	Remote Similarity	NPC253801
0.6914	Remote Similarity	NPC474790
0.6914	Remote Similarity	NPC39588
0.6914	Remote Similarity	NPC474976
0.6914	Remote Similarity	NPC144415
0.6912	Remote Similarity	NPC478095
0.6901	Remote Similarity	NPC471556
0.6892	Remote Similarity	NPC64234
0.6892	Remote Similarity	NPC37929
0.6892	Remote Similarity	NPC67183
0.6885	Remote Similarity	NPC128280
0.6885	Remote Similarity	NPC197467
0.6885	Remote Similarity	NPC100380
0.6883	Remote Similarity	NPC473223
0.6875	Remote Similarity	NPC25684
0.6875	Remote Similarity	NPC301477
0.6875	Remote Similarity	NPC281949
0.6867	Remote Similarity	NPC69082
0.6867	Remote Similarity	NPC473687
0.6867	Remote Similarity	NPC134885
0.6867	Remote Similarity	NPC134807
0.6867	Remote Similarity	NPC308412
0.6867	Remote Similarity	NPC210218
0.6867	Remote Similarity	NPC204686
0.6867	Remote Similarity	NPC219498
0.6867	Remote Similarity	NPC261721
0.6867	Remote Similarity	NPC279267
0.6866	Remote Similarity	NPC474825
0.686	Remote Similarity	NPC166110
0.6842	Remote Similarity	NPC470686
0.6842	Remote Similarity	NPC92558
0.6842	Remote Similarity	NPC20025
0.6842	Remote Similarity	NPC474758
0.6835	Remote Similarity	NPC469690
0.6829	Remote Similarity	NPC82297
0.6829	Remote Similarity	NPC149869
0.6829	Remote Similarity	NPC30486
0.6829	Remote Similarity	NPC475100
0.6824	Remote Similarity	NPC284561
0.6818	Remote Similarity	NPC228473
0.6818	Remote Similarity	NPC10316
0.6818	Remote Similarity	NPC200845
0.6818	Remote Similarity	NPC173157

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 NPC133904 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	156
0.1-0.2	2248
0.2-0.3	4399
0.3-0.4	1765
0.4-0.5	454
0.5-0.6	115
0.6-0.7	12
0.7-0.8	1
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
0.7	Intermediate Similarity	NPD5209	Approved
0.6984	Remote Similarity	NPD6927	Phase 3
0.6974	Remote Similarity	NPD8039	Approved
0.6795	Remote Similarity	NPD4756	Discovery
0.6761	Remote Similarity	NPD5325	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD2685	Clinical (unspecified phase)
0.6585	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.6548	Remote Similarity	NPD1694	Approved
0.6406	Remote Similarity	NPD4220	Pre-registration
0.6351	Remote Similarity	NPD6108	Clinical (unspecified phase)
0.6338	Remote Similarity	NPD4246	Clinical (unspecified phase)
0.625	Remote Similarity	NPD5343	Approved
0.6212	Remote Similarity	NPD28	Approved
0.6212	Remote Similarity	NPD29	Approved
0.618	Remote Similarity	NPD5785	Approved
0.6163	Remote Similarity	NPD1733	Clinical (unspecified phase)
0.6118	Remote Similarity	NPD7154	Phase 3
0.6087	Remote Similarity	NPD4627	Clinical (unspecified phase)
0.6087	Remote Similarity	NPD1698	Clinical (unspecified phase)
0.6053	Remote Similarity	NPD4247	Clinical (unspecified phase)
0.6032	Remote Similarity	NPD6097	Approved
0.6032	Remote Similarity	NPD6096	Approved
0.6029	Remote Similarity	NPD3172	Approved
0.6027	Remote Similarity	NPD4193	Approved
0.6027	Remote Similarity	NPD4194	Approved
0.6027	Remote Similarity	NPD4191	Approved
0.6027	Remote Similarity	NPD4192	Approved
0.6	Remote Similarity	NPD6698	Approved
0.6	Remote Similarity	NPD46	Approved
0.5977	Remote Similarity	NPD5363	Approved
0.5952	Remote Similarity	NPD4252	Approved
0.5942	Remote Similarity	NPD3194	Approved
0.5942	Remote Similarity	NPD3196	Approved
0.5942	Remote Similarity	NPD4266	Approved
0.5942	Remote Similarity	NPD3195	Phase 2
0.5938	Remote Similarity	NPD3174	Discontinued
0.593	Remote Similarity	NPD5362	Discontinued
0.5904	Remote Similarity	NPD5784	Clinical (unspecified phase)
0.5889	Remote Similarity	NPD1695	Approved
0.5867	Remote Similarity	NPD3197	Phase 1
0.5862	Remote Similarity	NPD6400	Clinical (unspecified phase)
0.5824	Remote Similarity	NPD7838	Discovery
0.5814	Remote Similarity	NPD4270	Approved
0.5814	Remote Similarity	NPD4269	Approved
0.5802	Remote Similarity	NPD4058	Approved
0.5802	Remote Similarity	NPD4687	Approved
0.5784	Remote Similarity	NPD2067	Discontinued
0.5765	Remote Similarity	NPD5790	Clinical (unspecified phase)
0.5761	Remote Similarity	NPD7983	Approved
0.575	Remote Similarity	NPD5276	Approved
0.5733	Remote Similarity	NPD2664	Clinical (unspecified phase)
0.5732	Remote Similarity	NPD1452	Discontinued
0.573	Remote Similarity	NPD6684	Approved
0.573	Remote Similarity	NPD7521	Approved
0.573	Remote Similarity	NPD7146	Approved
0.573	Remote Similarity	NPD5786	Approved
0.573	Remote Similarity	NPD5330	Approved
0.573	Remote Similarity	NPD6409	Approved
0.573	Remote Similarity	NPD7334	Approved
0.5714	Remote Similarity	NPD3704	Approved
0.5699	Remote Similarity	NPD5779	Approved
0.5699	Remote Similarity	NPD5778	Approved
0.5698	Remote Similarity	NPD5369	Approved
0.5672	Remote Similarity	NPD3173	Approved
0.5652	Remote Similarity	NPD5207	Approved
0.5632	Remote Similarity	NPD6435	Approved
0.561	Remote Similarity	NPD5733	Approved
0.5604	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.5604	Remote Similarity	NPD6672	Approved
0.5604	Remote Similarity	NPD6903	Approved
0.5604	Remote Similarity	NPD5737	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