NPASS Compound

Structure

NPC471595 OpenBabel07101719512D 23 23 0 0 1 0 0 0 0 0999 V2000 2.5981 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -4.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3660 2.3660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 1.5000 0.0000 C 0 0 3 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 -0.0000 3.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8660 1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 6 1 0 0 0 0 2 13 1 0 0 0 0 3 13 1 0 0 0 0 4 14 1 0 0 0 0 5 19 1 0 0 0 0 6 8 1 0 0 0 0 7 9 2 0 0 0 0 7 10 1 0 0 0 0 8 15 1 0 0 0 0 9 13 1 0 0 0 0 10 14 1 0 0 0 0 11 12 1 0 0 0 0 11 14 2 0 0 0 0 12 16 1 0 0 0 0 15 16 2 0 0 0 0 15 17 1 0 0 0 0 16 20 1 0 0 0 0 17 19 1 0 0 0 0 17 21 2 0 0 0 0 18 19 1 0 0 0 0 18 20 2 0 0 0 0 18 22 1 0 0 0 0 19 23 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	319.21
Volume:	352.809
LogP:	3.744
LogD:	4.201
LogS:	-4.264
# Rotatable Bonds:	7
TPSA:	66.73
# H-Bond Aceptor:	4
# H-Bond Donor:	1
# Rings:	1
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.577
Synthetic Accessibility Score:	4.655
Fsp3:	0.632
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
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:	-4.545
MDCK Permeability:	2.1052708689239807e-05
Pgp-inhibitor:	0.218
Pgp-substrate:	0.003
Human Intestinal Absorption (HIA):	0.04
20% Bioavailability (F20%):	0.006
30% Bioavailability (F30%):	0.007

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.939
Plasma Protein Binding (PPB):	97.35326385498047%
Volume Distribution (VD):	1.293
Pgp-substrate:	2.2415146827697754%

ADMET: Metabolism

CYP1A2-inhibitor:	0.031
CYP1A2-substrate:	0.171
CYP2C19-inhibitor:	0.057
CYP2C19-substrate:	0.933
CYP2C9-inhibitor:	0.048
CYP2C9-substrate:	0.441
CYP2D6-inhibitor:	0.004
CYP2D6-substrate:	0.122
CYP3A4-inhibitor:	0.814
CYP3A4-substrate:	0.91

ADMET: Excretion

Clearance (CL):	4.245
Half-life (T1/2):	0.663

ADMET: Toxicity

hERG Blockers:	0.01
Human Hepatotoxicity (H-HT):	0.225
Drug-inuced Liver Injury (DILI):	0.866
AMES Toxicity:	0.018
Rat Oral Acute Toxicity:	0.466
Maximum Recommended Daily Dose:	0.751
Skin Sensitization:	0.268
Carcinogencity:	0.885
Eye Corrosion:	0.004
Eye Irritation:	0.014
Respiratory Toxicity:	0.958

Download Data

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

Natural Product: NPC471595

Natural Product ID:	NPC471595
*Common Name:**	Iromycin F
IUPAC Name:	6-[(2E,5E)-3,7-dimethylocta-2,5-dienyl]-3-hydroxy-3-methyl-5-propyl-1H-pyridine-2,4-dione
Synonyms:
Standard InCHIKey:	CFXXCKIWSIISPX-DTCTWCMCSA-N
Standard InCHI:	InChI=1S/C19H29NO3/c1-6-8-15-16(20-18(22)19(5,23)17(15)21)12-11-14(4)10-7-9-13(2)3/h7,9,11,13,23H,6,8,10,12H2,1-5H3,(H,20,22)/b9-7+,14-11+
SMILES:	CCCC1=C(NC(=O)C(C1=O)(C)O)CC=C(C)CC=CC(C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL272059
PubChem CID:	44456321
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001549] Monoterpenoids [CHEMONTID:0001563] Monocyclic monoterpenoids

*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
NPO33217	streptomyces sp. dra 17	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[18054490]

☑ 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
Protein Complex	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT5098	Protein Complex	Mitochondrial complex I; NADH oxidoreductase	Bos taurus	IC50	>	25300.0	nM	PMID[528376]

☑ 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 NPC471595 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	77
0.1-0.2	592
0.2-0.3	11067
0.3-0.4	20678
0.4-0.5	8759
0.5-0.6	1455
0.6-0.7	67
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.7241	Intermediate Similarity	NPC471597
0.6989	Remote Similarity	NPC472614
0.6796	Remote Similarity	NPC472616
0.6731	Remote Similarity	NPC472615
0.6703	Remote Similarity	NPC275766
0.6633	Remote Similarity	NPC472613
0.6571	Remote Similarity	NPC271269
0.6531	Remote Similarity	NPC314500
0.6509	Remote Similarity	NPC251330
0.6421	Remote Similarity	NPC79573
0.6389	Remote Similarity	NPC133729
0.6383	Remote Similarity	NPC477786
0.6383	Remote Similarity	NPC477785
0.6383	Remote Similarity	NPC477784
0.6374	Remote Similarity	NPC478122
0.6372	Remote Similarity	NPC296361
0.6348	Remote Similarity	NPC315915
0.6306	Remote Similarity	NPC5485
0.6304	Remote Similarity	NPC477485
0.6296	Remote Similarity	NPC307903
0.6296	Remote Similarity	NPC140251
0.6286	Remote Similarity	NPC128501
0.6283	Remote Similarity	NPC271621
0.6283	Remote Similarity	NPC59751
0.6283	Remote Similarity	NPC27413
0.6277	Remote Similarity	NPC477487
0.6273	Remote Similarity	NPC170375
0.6265	Remote Similarity	NPC477830
0.6264	Remote Similarity	NPC477484
0.6264	Remote Similarity	NPC477486
0.6262	Remote Similarity	NPC154601
0.6235	Remote Similarity	NPC197089
0.6235	Remote Similarity	NPC137163
0.6211	Remote Similarity	NPC475083
0.6207	Remote Similarity	NPC469914
0.6196	Remote Similarity	NPC248624
0.6196	Remote Similarity	NPC469492
0.6195	Remote Similarity	NPC315652
0.6195	Remote Similarity	NPC7905
0.6186	Remote Similarity	NPC472009
0.6186	Remote Similarity	NPC472136
0.6186	Remote Similarity	NPC472161
0.617	Remote Similarity	NPC67254
0.614	Remote Similarity	NPC316325
0.6132	Remote Similarity	NPC469598
0.6129	Remote Similarity	NPC469517
0.6129	Remote Similarity	NPC314854
0.6129	Remote Similarity	NPC313911
0.6122	Remote Similarity	NPC472007
0.6121	Remote Similarity	NPC473808
0.6111	Remote Similarity	NPC122244
0.6106	Remote Similarity	NPC476814
0.6106	Remote Similarity	NPC476813
0.6098	Remote Similarity	NPC278202
0.6082	Remote Similarity	NPC187529
0.6075	Remote Similarity	NPC474563
0.6071	Remote Similarity	NPC53109
0.6071	Remote Similarity	NPC143168
0.6061	Remote Similarity	NPC116231
0.6061	Remote Similarity	NPC472008
0.6061	Remote Similarity	NPC316186
0.6023	Remote Similarity	NPC262673
0.6022	Remote Similarity	NPC207772
0.6022	Remote Similarity	NPC231739
0.6	Remote Similarity	NPC474353
0.6	Remote Similarity	NPC234542
0.6	Remote Similarity	NPC225515
0.6	Remote Similarity	NPC7029
0.5976	Remote Similarity	NPC320421
0.5962	Remote Similarity	NPC123141
0.596	Remote Similarity	NPC476079
0.596	Remote Similarity	NPC113370
0.596	Remote Similarity	NPC103743
0.5957	Remote Similarity	NPC113363
0.5955	Remote Similarity	NPC94743
0.5955	Remote Similarity	NPC291062
0.5952	Remote Similarity	NPC64971
0.5946	Remote Similarity	NPC24389
0.5943	Remote Similarity	NPC473224
0.5941	Remote Similarity	NPC469464
0.593	Remote Similarity	NPC61473
0.5929	Remote Similarity	NPC476269
0.5922	Remote Similarity	NPC116930
0.5918	Remote Similarity	NPC307112
0.5914	Remote Similarity	NPC476007
0.5909	Remote Similarity	NPC476614
0.5905	Remote Similarity	NPC472166
0.5895	Remote Similarity	NPC108955
0.5895	Remote Similarity	NPC472948
0.5889	Remote Similarity	NPC126061
0.5882	Remote Similarity	NPC477707
0.587	Remote Similarity	NPC199445
0.587	Remote Similarity	NPC77501
0.587	Remote Similarity	NPC114236
0.5859	Remote Similarity	NPC203795
0.5851	Remote Similarity	NPC471409
0.5851	Remote Similarity	NPC275494
0.5843	Remote Similarity	NPC477448
0.5843	Remote Similarity	NPC474060
0.5843	Remote Similarity	NPC250928
0.5843	Remote Similarity	NPC477449
0.5843	Remote Similarity	NPC10758
0.5833	Remote Similarity	NPC55869
0.5833	Remote Similarity	NPC477582
0.5816	Remote Similarity	NPC90446
0.5816	Remote Similarity	NPC477199
0.5806	Remote Similarity	NPC110725
0.58	Remote Similarity	NPC23622
0.5798	Remote Similarity	NPC469515
0.5795	Remote Similarity	NPC243272
0.5795	Remote Similarity	NPC278895
0.5785	Remote Similarity	NPC469494
0.5784	Remote Similarity	NPC477684
0.5784	Remote Similarity	NPC475879
0.5783	Remote Similarity	NPC281195
0.5778	Remote Similarity	NPC203819
0.5778	Remote Similarity	NPC318766
0.5773	Remote Similarity	NPC477583
0.5773	Remote Similarity	NPC477581
0.5766	Remote Similarity	NPC475800
0.5765	Remote Similarity	NPC21848
0.5765	Remote Similarity	NPC64985
0.5765	Remote Similarity	NPC124849
0.5761	Remote Similarity	NPC264178
0.5761	Remote Similarity	NPC160540
0.5761	Remote Similarity	NPC469835
0.5761	Remote Similarity	NPC7382
0.5761	Remote Similarity	NPC147438
0.5758	Remote Similarity	NPC469993
0.5758	Remote Similarity	NPC33663
0.5755	Remote Similarity	NPC265662
0.5755	Remote Similarity	NPC471694
0.5755	Remote Similarity	NPC473161
0.5752	Remote Similarity	NPC476290
0.5747	Remote Similarity	NPC474304
0.5747	Remote Similarity	NPC474329
0.5745	Remote Similarity	NPC266124
0.5745	Remote Similarity	NPC211279
0.5743	Remote Similarity	NPC269677
0.5743	Remote Similarity	NPC58271
0.5743	Remote Similarity	NPC476708
0.5741	Remote Similarity	NPC175531
0.5741	Remote Similarity	NPC313234
0.573	Remote Similarity	NPC146376
0.573	Remote Similarity	NPC125578
0.573	Remote Similarity	NPC263382
0.5729	Remote Similarity	NPC824
0.5729	Remote Similarity	NPC476809
0.5729	Remote Similarity	NPC138492
0.5729	Remote Similarity	NPC30675
0.5729	Remote Similarity	NPC233352
0.5727	Remote Similarity	NPC14537
0.5726	Remote Similarity	NPC476190
0.5714	Remote Similarity	NPC84790
0.5714	Remote Similarity	NPC106309
0.5714	Remote Similarity	NPC288667
0.5714	Remote Similarity	NPC16488
0.5714	Remote Similarity	NPC469836
0.57	Remote Similarity	NPC261721
0.57	Remote Similarity	NPC262026
0.57	Remote Similarity	NPC196381
0.57	Remote Similarity	NPC94666
0.5699	Remote Similarity	NPC175079
0.5699	Remote Similarity	NPC251435
0.5699	Remote Similarity	NPC89374
0.5699	Remote Similarity	NPC474885
0.5698	Remote Similarity	NPC190049
0.5698	Remote Similarity	NPC322457
0.5684	Remote Similarity	NPC178852
0.5684	Remote Similarity	NPC121200
0.5684	Remote Similarity	NPC321180
0.5684	Remote Similarity	NPC19443
0.5684	Remote Similarity	NPC475994
0.5682	Remote Similarity	NPC16119
0.5682	Remote Similarity	NPC142423
0.5682	Remote Similarity	NPC472072
0.5682	Remote Similarity	NPC308294
0.5676	Remote Similarity	NPC473252
0.5676	Remote Similarity	NPC469852
0.5673	Remote Similarity	NPC469645
0.5673	Remote Similarity	NPC469692
0.567	Remote Similarity	NPC112868
0.567	Remote Similarity	NPC44963
0.567	Remote Similarity	NPC472684
0.567	Remote Similarity	NPC116797
0.567	Remote Similarity	NPC14151
0.567	Remote Similarity	NPC470298
0.567	Remote Similarity	NPC189237
0.5667	Remote Similarity	NPC94488
0.5664	Remote Similarity	NPC473578
0.5664	Remote Similarity	NPC474725
0.5663	Remote Similarity	NPC192843
0.5663	Remote Similarity	NPC281230
0.566	Remote Similarity	NPC473291
0.5657	Remote Similarity	NPC144258
0.5652	Remote Similarity	NPC186042
0.5652	Remote Similarity	NPC12815
0.5652	Remote Similarity	NPC238948
0.5652	Remote Similarity	NPC215745
0.5652	Remote Similarity	NPC300940

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 NPC471595 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	83
0.1-0.2	698
0.2-0.3	4585
0.3-0.4	3108
0.4-0.5	599
0.5-0.6	71
0.6-0.7	6
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
0.6273	Remote Similarity	NPD7601	Clinical (unspecified phase)
0.6273	Remote Similarity	NPD7116	Clinical (unspecified phase)
0.6235	Remote Similarity	NPD7331	Phase 2
0.6207	Remote Similarity	NPD15	Approved
0.6207	Remote Similarity	NPD1082	Approved
0.6207	Remote Similarity	NPD791	Approved
0.6154	Remote Similarity	NPD819	Approved
0.6154	Remote Similarity	NPD818	Approved
0.614	Remote Similarity	NPD7500	Approved
0.6071	Remote Similarity	NPD2664	Clinical (unspecified phase)
0.5978	Remote Similarity	NPD1346	Approved
0.5941	Remote Similarity	NPD790	Approved
0.593	Remote Similarity	NPD7341	Phase 2
0.5895	Remote Similarity	NPD4695	Discontinued
0.5773	Remote Similarity	NPD4800	Clinical (unspecified phase)
0.5769	Remote Similarity	NPD5282	Discontinued
0.5765	Remote Similarity	NPD835	Approved
0.5765	Remote Similarity	NPD834	Approved
0.575	Remote Similarity	NPD7623	Phase 3
0.575	Remote Similarity	NPD7624	Clinical (unspecified phase)
0.5714	Remote Similarity	NPD7299	Clinical (unspecified phase)
0.57	Remote Similarity	NPD5690	Phase 2
0.5682	Remote Similarity	NPD6108	Clinical (unspecified phase)
0.5667	Remote Similarity	NPD7739	Clinical (unspecified phase)
0.5657	Remote Similarity	NPD4197	Approved
0.56	Remote Similarity	NPD5329	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