NPASS Compound

Natural Product: NPC582475

Natural Product ID	NPC582475
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Diethyl hexadecanedioate
IUPAC Name	diethyl hexadecanedioate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 62 61 0 0 0 0 0 0 0 0999 V2000 -8.6990 2.8090 -0.4831 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6079 1.3283 -0.6804 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2601 0.8614 -0.5118 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.9675 -0.4854 -0.6535 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9167 -1.2608 -0.9304 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5561 -0.9918 -0.4794 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3647 -1.6141 0.8587 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9530 -2.1243 1.0010 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9802 -1.0125 0.8707 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5539 -1.5341 1.0603 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2392 -2.5695 0.0219 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1597 -3.0687 0.2152 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1654 -1.9670 0.0979 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0822 -1.3287 -1.2436 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1257 -0.2414 -1.3537 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9921 0.8596 -0.3601 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0420 1.9275 -0.5404 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4172 1.3722 -0.3755 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4845 2.4420 -0.5429 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7936 1.7586 -0.3564 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3265 1.0644 -1.2569 O 0 0 0 0 0 0 0 0 0 0 0 0 7.4629 1.8813 0.8468 O 0 0 0 0 0 0 0 0 0 0 0 0 8.7030 1.2258 1.0039 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6477 1.7671 -0.0394 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5283 3.0102 0.2480 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0141 3.3065 -1.4230 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7357 3.2393 -0.1382 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2749 0.7618 0.0121 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8888 1.0553 -1.7199 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4243 -1.7834 -1.2472 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8370 -0.1992 -0.7255 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0238 -2.5138 1.0014 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5779 -0.9196 1.7038 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8291 -2.7170 1.9293 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7880 -2.8122 0.1153 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1396 -0.1873 1.5925 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9888 -0.5379 -0.1367 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8544 -0.6755 0.9254 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5168 -1.9296 2.0896 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3649 -2.2053 -1.0069 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9300 -3.4685 0.1734 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4418 -3.8456 -0.5319 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2667 -3.5102 1.2329 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0529 -1.1993 0.8856 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2101 -2.3712 0.1924 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0812 -0.9123 -1.4896 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3041 -2.0442 -2.0756 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0633 0.1252 -2.4106 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1223 -0.7349 -1.2925 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0717 0.4745 0.6782 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9955 1.3465 -0.4365 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9231 2.3774 -1.5612 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8163 2.7363 0.1987 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6396 0.5083 -1.0261 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5198 1.0085 0.6859 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4068 2.9518 -1.5227 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3404 3.1905 0.2505 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5150 0.1397 0.8749 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0558 1.4612 2.0327 H 0 0 0 0 0 0 0 0 0 0 0 0 10.6750 1.9121 0.3558 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2769 2.7592 -0.3541 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6337 1.1038 -0.9284 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 2 0 4 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 2 0 20 22 1 0 22 23 1 0 23 24 1 0 1 25 1 0 1 26 1 0 1 27 1 0 2 28 1 0 2 29 1 0 6 30 1 0 6 31 1 0 7 32 1 0 7 33 1 0 8 34 1 0 8 35 1 0 9 36 1 0 9 37 1 0 10 38 1 0 10 39 1 0 11 40 1 0 11 41 1 0 12 42 1 0 12 43 1 0 13 44 1 0 13 45 1 0 14 46 1 0 14 47 1 0 15 48 1 0 15 49 1 0 16 50 1 0 16 51 1 0 17 52 1 0 17 53 1 0 18 54 1 0 18 55 1 0 19 56 1 0 19 57 1 0 23 58 1 0 23 59 1 0 24 60 1 0 24 61 1 0 24 62 1 0 M END

Standard InCHIKey	AHIOKFKBLGHSSV-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C20H38O4/c1-3-23-19(21)17-15-13-11-9-7-5-6-8-10-12-14-16-18-20(22)24-4-2/h3-18H2,1-2H3
SMILES	CCOC(=O)CCCCCCCCCCCCCCC(=O)OCC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	342.28	Volume:	384.364 ? Van der Waals volume.
Dense:	0.891	LogP:	4.989 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.366 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.871 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	19.0	Rigid Bonds:	2.0
TPSA:	52.6 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	0.0	Rings:	0.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.256	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	1.721	Fsp³:	0.9
MCE-18:	0.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.022	Fluc inhibitor:	0.009 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.003 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.994	Promiscuous compounds:	0.411

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.062	MDCK Permeability:	-4.693
Pgp-inhibitor:	0.036	Pgp-substrate:	0.006
PAMPA:	0.003 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.01
20% Bioavailability (F20%):	0.857	30% Bioavailability (F30%):	0.857
50% Bioavailability (F50%):	0.965

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	1.0
Plasma Protein Binding (PPB):	96.622%	Volume Distribution (VD):	0.096
Fu:	3.71% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.018
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.103
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.016	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.02
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.957
CYP3A4-inhibitor:	0.06	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.061	CYP2C8-inhibitor:	1.0
HLM stability:	0.999 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

5.595

Half-life (T1/2):

0.453

ADMET: Toxicity

hERG Blockers:	0.165	hERG Blockers (10um):	0.631
Human Hepatotoxicity (H-HT):	0.167	Drug-induced Liver Injury (DILI):	0.147
AMES Toxicity:	0.04	Rat Oral Acute Toxicity:	0.026
Maximum Recommended Daily Dose:	0.06	Skin Sensitization:	0.958
Carcinogencity:	0.53	Eye Corrosion:	0.943
Eye Irritation:	0.997	Respiratory Toxicity:	0.457
Drug-induced Neurotoxicity:	0.007	Ototoxicity:	0.104
Hematotoxicity:	0.095	Drug-induced Nephrotoxicity:	0.127
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.023
A549 Cytotoxicity:	0.005	Hek293 Cytotoxicity:	0.013
BCF:	1.2 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	4.626 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.115 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.887 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO51770	Garcinia indica	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39680751]
NPO51770	Garcinia indica	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference
NPO51770	Garcinia indica	Ethanolic extract	Fruits	0.63	n.a.	n.a.	%	PMID[39680751]

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

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

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 toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC582475 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	26354
0.1-0.2	21978
0.2-0.3	1295
0.3-0.4	119
0.4-0.5	55
0.5-0.6	36
0.6-0.7	10
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	6
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC53541
0.9	High Similarity	NPC250028
0.9	High Similarity	NPC236579
0.9	High Similarity	NPC80234
0.9	High Similarity	NPC203531
0.9	High Similarity	NPC256163
0.9	High Similarity	NPC40597
0.7	Intermediate Similarity	NPC143211
0.6923	Remote Similarity	NPC128061
0.6522	Remote Similarity	NPC81263
0.64	Remote Similarity	NPC603612
0.6316	Remote Similarity	NPC32280
0.625	Remote Similarity	NPC223249
0.6207	Remote Similarity	NPC10316
0.6207	Remote Similarity	NPC200845
0.6207	Remote Similarity	NPC28779
0.6154	Remote Similarity	NPC149299
0.6154	Remote Similarity	NPC310746
0.5926	Remote Similarity	NPC26253
0.5769	Remote Similarity	NPC80396
0.5769	Remote Similarity	NPC154642
0.5769	Remote Similarity	NPC600941
0.5714	Remote Similarity	NPC488257
0.5714	Remote Similarity	NPC469937
0.5714	Remote Similarity	NPC94699
0.5714	Remote Similarity	NPC99700
0.5714	Remote Similarity	NPC320588
0.5714	Remote Similarity	NPC219536
0.5714	Remote Similarity	NPC53463
0.5714	Remote Similarity	NPC31551
0.5652	Remote Similarity	NPC201622
0.5652	Remote Similarity	NPC305660
0.5652	Remote Similarity	NPC12156
0.5652	Remote Similarity	NPC161097
0.5652	Remote Similarity	NPC28598
0.5652	Remote Similarity	NPC22903
0.5652	Remote Similarity	NPC54980
0.5625	Remote Similarity	NPC188686
0.56	Remote Similarity	NPC476550
0.5517	Remote Similarity	NPC55678
0.55	Remote Similarity	NPC327450
0.55	Remote Similarity	NPC234005
0.5385	Remote Similarity	NPC286695
0.5294	Remote Similarity	NPC143857
0.5294	Remote Similarity	NPC229252
0.5238	Remote Similarity	NPC57499
0.5217	Remote Similarity	NPC21374
0.52	Remote Similarity	NPC47363
0.52	Remote Similarity	NPC287231
0.52	Remote Similarity	NPC317128
0.5185	Remote Similarity	NPC80641
0.5172	Remote Similarity	NPC308301
0.5161	Remote Similarity	NPC223677
0.5161	Remote Similarity	NPC609455

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC582475 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6610
0.1-0.2	2358
0.2-0.3	151
0.3-0.4	19
0.4-0.5	8
0.5-0.6	4
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
0.5517	Remote Similarity	NPD5343	Phase 4
0.5517	Remote Similarity	NPD6125	Phase 4
0.52	Remote Similarity	NPD2699	Pre-clinical
0.5161	Remote Similarity	NPD6096	Phase 4

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by 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