NPASS Compound

Structure

NPC74617 OpenBabel07101718242D 21 21 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 3.0981 -9.3660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5981 -8.5000 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 -0.0000 -4.0000 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 -4.5000 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 -5.5000 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 0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -7.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0000 -1.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.7321 -6.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -8.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -7.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -5.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -9.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2 16 1 0 0 0 0 3 16 1 0 0 0 0 4 5 1 0 0 0 0 4 6 1 0 0 0 0 5 7 1 0 0 0 0 6 8 2 0 0 0 0 7 9 2 0 0 0 0 9 15 1 0 0 0 0 10 11 2 0 0 0 0 10 13 1 0 0 0 0 11 14 1 0 0 0 0 12 16 1 0 0 0 0 12 17 1 0 0 0 0 13 1 1 1 0 0 0 13 20 1 0 0 0 0 14 8 1 1 0 0 0 14 21 1 0 0 0 0 15 17 2 3 0 0 0 15 18 1 0 0 0 0 16 19 1 0 0 0 0 20 21 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	295.18
Volume:	312.348
LogP:	1.292
LogD:	1.015
LogS:	-1.975
# Rotatable Bonds:	8
TPSA:	67.79
# H-Bond Aceptor:	5
# H-Bond Donor:	2
# Rings:	1
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.557
Synthetic Accessibility Score:	4.473
Fsp3:	0.562
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:	-4.619
MDCK Permeability:	1.6213081835303456e-05
Pgp-inhibitor:	0.0
Pgp-substrate:	0.002
Human Intestinal Absorption (HIA):	0.009
20% Bioavailability (F20%):	0.022
30% Bioavailability (F30%):	0.982

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.951
Plasma Protein Binding (PPB):	42.3322868347168%
Volume Distribution (VD):	1.176
Pgp-substrate:	49.90963363647461%

ADMET: Metabolism

CYP1A2-inhibitor:	0.058
CYP1A2-substrate:	0.267
CYP2C19-inhibitor:	0.23
CYP2C19-substrate:	0.473
CYP2C9-inhibitor:	0.21
CYP2C9-substrate:	0.175
CYP2D6-inhibitor:	0.019
CYP2D6-substrate:	0.204
CYP3A4-inhibitor:	0.333
CYP3A4-substrate:	0.283

ADMET: Excretion

Clearance (CL):	7.224
Half-life (T1/2):	0.846

ADMET: Toxicity

hERG Blockers:	0.017
Human Hepatotoxicity (H-HT):	0.474
Drug-inuced Liver Injury (DILI):	0.135
AMES Toxicity:	0.981
Rat Oral Acute Toxicity:	0.019
Maximum Recommended Daily Dose:	0.028
Skin Sensitization:	0.259
Carcinogencity:	0.118
Eye Corrosion:	0.004
Eye Irritation:	0.024
Respiratory Toxicity:	0.1

Download Data

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

Natural Product: NPC74617

Natural Product ID:	NPC74617
*Common Name:**	Timuramide A
IUPAC Name:	(2E,6Z)-N-(2-hydroxy-2-methylpropyl)-7-[(3R,6S)-6-methyl-3,6-dihydro-1,2-dioxin-3-yl]hepta-2,6-dienamide
Synonyms:	timuramide A
Standard InCHIKey:	UVKRYXUFGIPFLZ-WLGKPCDOSA-N
Standard InCHI:	InChI=1S/C16H25NO4/c1-13-10-11-14(21-20-13)8-6-4-5-7-9-15(18)17-12-16(2,3)19/h6-11,13-14,19H,4-5,12H2,1-3H3,(H,17,18)/b8-6-,9-7+/t13-,14+/m0/s1
SMILES:	C[C@@H]1OO[C@@H](C=C1)/C=CCC/C=C/C(=NCC(O)(C)C)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL2335718
PubChem CID:	71521889
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0000331] Fatty amides [CHEMONTID:0001096] N-acyl amines

*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
NPO33007	nepalese zanthoxylum armatum	Species	n.a.	n.a.	pericarp	n.a.	n.a.	PMID[23268719]

☑ 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	2

Activity Type	# Activity
NON-MOLECULAR	1
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	GI	=	38.0	%	PMID[453888]
NPT27	Others	Unspecified		Activity	=	97.0	%	PMID[453888]

☑ 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 NPC74617 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	44
0.1-0.2	5622
0.2-0.3	25830
0.3-0.4	9295
0.4-0.5	1498
0.5-0.6	317
0.6-0.7	52
0.7-0.8	28
0.8-0.85	9
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC150505
0.8525	High Similarity	NPC471023
0.8421	Intermediate Similarity	NPC14234
0.8421	Intermediate Similarity	NPC269800
0.8421	Intermediate Similarity	NPC132669
0.8421	Intermediate Similarity	NPC246519
0.8421	Intermediate Similarity	NPC44193
0.8421	Intermediate Similarity	NPC184014
0.8387	Intermediate Similarity	NPC253468
0.8387	Intermediate Similarity	NPC235311
0.7761	Intermediate Similarity	NPC471022
0.7742	Intermediate Similarity	NPC312826
0.7586	Intermediate Similarity	NPC267340
0.7586	Intermediate Similarity	NPC304223
0.7586	Intermediate Similarity	NPC54542
0.7586	Intermediate Similarity	NPC243539
0.7586	Intermediate Similarity	NPC145032
0.75	Intermediate Similarity	NPC273614
0.7414	Intermediate Similarity	NPC267692
0.7414	Intermediate Similarity	NPC307435
0.7385	Intermediate Similarity	NPC77891
0.7344	Intermediate Similarity	NPC130807
0.7333	Intermediate Similarity	NPC303672
0.7333	Intermediate Similarity	NPC119655
0.7313	Intermediate Similarity	NPC129995
0.7313	Intermediate Similarity	NPC315141
0.7213	Intermediate Similarity	NPC167759
0.7213	Intermediate Similarity	NPC305288
0.7213	Intermediate Similarity	NPC56028
0.7213	Intermediate Similarity	NPC163912
0.7167	Intermediate Similarity	NPC195986
0.7164	Intermediate Similarity	NPC477525
0.7097	Intermediate Similarity	NPC273023
0.7097	Intermediate Similarity	NPC297020
0.7097	Intermediate Similarity	NPC471991
0.7097	Intermediate Similarity	NPC471992
0.7077	Intermediate Similarity	NPC6795
0.6984	Remote Similarity	NPC477049
0.6984	Remote Similarity	NPC261158
0.6984	Remote Similarity	NPC24216
0.6984	Remote Similarity	NPC306420
0.6984	Remote Similarity	NPC104138
0.697	Remote Similarity	NPC29468
0.6964	Remote Similarity	NPC86121
0.6944	Remote Similarity	NPC314678
0.6935	Remote Similarity	NPC123669
0.6935	Remote Similarity	NPC124382
0.6935	Remote Similarity	NPC13011
0.6875	Remote Similarity	NPC245650
0.6825	Remote Similarity	NPC242930
0.6761	Remote Similarity	NPC291196
0.6761	Remote Similarity	NPC103712
0.6622	Remote Similarity	NPC288086
0.662	Remote Similarity	NPC249713
0.6618	Remote Similarity	NPC477106
0.6571	Remote Similarity	NPC187315
0.6515	Remote Similarity	NPC321030
0.6418	Remote Similarity	NPC329003
0.6418	Remote Similarity	NPC326524
0.6418	Remote Similarity	NPC325550
0.6377	Remote Similarity	NPC182758
0.6324	Remote Similarity	NPC309877
0.6301	Remote Similarity	NPC280065
0.6301	Remote Similarity	NPC45060
0.6232	Remote Similarity	NPC324077
0.623	Remote Similarity	NPC91044
0.6143	Remote Similarity	NPC55068
0.6104	Remote Similarity	NPC476924
0.6102	Remote Similarity	NPC470439
0.6098	Remote Similarity	NPC228638
0.6049	Remote Similarity	NPC82799
0.6032	Remote Similarity	NPC474460
0.6029	Remote Similarity	NPC325734
0.5902	Remote Similarity	NPC160628
0.5897	Remote Similarity	NPC217095
0.5897	Remote Similarity	NPC264417
0.5873	Remote Similarity	NPC31194
0.5873	Remote Similarity	NPC153538
0.5873	Remote Similarity	NPC248884
0.5873	Remote Similarity	NPC85079
0.5833	Remote Similarity	NPC116934
0.5806	Remote Similarity	NPC282097
0.5806	Remote Similarity	NPC124183
0.5806	Remote Similarity	NPC35141
0.5802	Remote Similarity	NPC314854
0.5802	Remote Similarity	NPC313911
0.5797	Remote Similarity	NPC210999
0.5789	Remote Similarity	NPC324638
0.5781	Remote Similarity	NPC328784
0.5781	Remote Similarity	NPC291437
0.5781	Remote Similarity	NPC72699
0.5765	Remote Similarity	NPC3210
0.5763	Remote Similarity	NPC269823
0.5747	Remote Similarity	NPC316186
0.5738	Remote Similarity	NPC138935
0.5735	Remote Similarity	NPC4881
0.5696	Remote Similarity	NPC476923
0.5694	Remote Similarity	NPC316674
0.5692	Remote Similarity	NPC473672
0.5692	Remote Similarity	NPC55383
0.5692	Remote Similarity	NPC93639
0.5692	Remote Similarity	NPC71053
0.5692	Remote Similarity	NPC474495
0.5692	Remote Similarity	NPC59408
0.5692	Remote Similarity	NPC151782
0.569	Remote Similarity	NPC255042
0.569	Remote Similarity	NPC29091
0.569	Remote Similarity	NPC15934
0.569	Remote Similarity	NPC182840
0.569	Remote Similarity	NPC103213
0.5679	Remote Similarity	NPC474833
0.5667	Remote Similarity	NPC213538
0.5667	Remote Similarity	NPC256766
0.5652	Remote Similarity	NPC175614
0.5645	Remote Similarity	NPC140501
0.5625	Remote Similarity	NPC471275
0.5625	Remote Similarity	NPC471280
0.5625	Remote Similarity	NPC125122
0.5625	Remote Similarity	NPC471276
0.5625	Remote Similarity	NPC267110
0.5618	Remote Similarity	NPC242503
0.5618	Remote Similarity	NPC74672
0.5618	Remote Similarity	NPC139782
0.5618	Remote Similarity	NPC43074
0.5618	Remote Similarity	NPC209047
0.561	Remote Similarity	NPC471597
0.5606	Remote Similarity	NPC142092
0.5606	Remote Similarity	NPC35756
0.5604	Remote Similarity	NPC23454
0.5604	Remote Similarity	NPC35269
0.5604	Remote Similarity	NPC256570
0.5604	Remote Similarity	NPC70323
0.5604	Remote Similarity	NPC192066
0.5604	Remote Similarity	NPC17290
0.5604	Remote Similarity	NPC262312
0.5604	Remote Similarity	NPC3568

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 NPC74617 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	53
0.1-0.2	1585
0.2-0.3	6084
0.3-0.4	1298
0.4-0.5	114
0.5-0.6	15
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
0.6167	Remote Similarity	NPD860	Phase 2
0.6143	Remote Similarity	NPD3210	Clinical (unspecified phase)
0.5797	Remote Similarity	NPD9368	Phase 2
0.5795	Remote Similarity	NPD6094	Approved
0.5795	Remote Similarity	NPD6095	Approved
0.5789	Remote Similarity	NPD3212	Clinical (unspecified phase)
0.5714	Remote Similarity	NPD205	Approved
0.5645	Remote Similarity	NPD4265	Approved
0.5618	Remote Similarity	NPD8522	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