NPASS Compound

Natural Product: NPC68743

Natural Product ID	NPC68743
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Trimethyl 2-Hydroxypropane-1,2,3-Tricarboxylate
IUPAC Name	trimethyl 2-hydroxypropane-1,2,3-tricarboxylate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL455514
PubChem CID	74112
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0001986] Tricarboxylic acids and derivatives

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 30 29 0 0 0 0 0 0 0 0999 V2000 1.8856 -3.5162 -0.6308 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0377 -2.5635 -0.0162 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5283 -1.5456 -0.7831 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8046 -1.4603 -1.9933 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3612 -0.5385 -0.1566 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2065 0.8650 -0.3515 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5590 0.9574 0.2737 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1248 0.0128 0.8647 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2284 2.1692 0.1923 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5135 2.3746 0.7476 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6815 -0.6541 -0.8439 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7333 0.2463 -0.3791 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8361 0.1974 -1.0098 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6525 1.1308 0.6602 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7332 1.9587 1.0290 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5224 -0.8322 1.1849 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7966 -4.5237 -0.1876 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6809 -3.5292 -1.7365 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9558 -3.2097 -0.4878 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4335 1.5515 0.2282 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2422 1.0542 -1.4275 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5667 3.4597 1.0458 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3315 2.1994 0.0137 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6732 1.7554 1.6639 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0471 -1.7022 -0.6623 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5457 -0.5691 -1.9420 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6728 2.2402 2.0983 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6804 1.3929 0.9019 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7335 2.8953 0.4070 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5022 -1.8163 1.2969 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 3 5 1 0 5 6 1 0 6 7 1 0 7 8 2 0 7 9 1 0 9 10 1 0 5 11 1 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 1 0 5 16 1 0 1 17 1 0 1 18 1 0 1 19 1 0 6 20 1 0 6 21 1 0 10 22 1 0 10 23 1 0 10 24 1 0 11 25 1 0 11 26 1 0 15 27 1 0 15 28 1 0 15 29 1 0 16 30 1 0 M END

Standard InCHIKey	HDDLVZWGOPWKFW-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C9H14O7/c1-14-6(10)4-9(13,8(12)16-3)5-7(11)15-2/h13H,4-5H2,1-3H3
SMILES	COC(=O)C(CC(=O)OC)(CC(=O)OC)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	234.07	Volume:	217.843 ? Van der Waals volume.
Dense:	1.074	LogP:	-0.381 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.216 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-0.574 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	3.0
TPSA:	99.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	1.0	Rings:	0.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.482	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.537	Fsp³:	0.667
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:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.005	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.016 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.083 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.974	Promiscuous compounds:	0.014

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.786	MDCK Permeability:	-4.603
Pgp-inhibitor:	0.001	Pgp-substrate:	0.242
PAMPA:	0.873 ? 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):	0.113
20% Bioavailability (F20%):	0.722	30% Bioavailability (F30%):	0.825
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.064	MRP1:	0.849
Plasma Protein Binding (PPB):	4.12%	Volume Distribution (VD):	-0.026
Fu:	98.926% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.912
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.005
BSEP inhibitor:	0.789

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.936
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.716	CYP3A4-substrate:	0.002
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.908
HLM stability:	1.0 ? 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):

8.188

Half-life (T1/2):

0.862

ADMET: Toxicity

hERG Blockers:	0.015	hERG Blockers (10um):	0.224
Human Hepatotoxicity (H-HT):	0.329	Drug-induced Liver Injury (DILI):	0.195
AMES Toxicity:	0.11	Rat Oral Acute Toxicity:	0.374
Maximum Recommended Daily Dose:	0.227	Skin Sensitization:	0.284
Carcinogencity:	0.102	Eye Corrosion:	0.005
Eye Irritation:	0.31	Respiratory Toxicity:	0.126
Drug-induced Neurotoxicity:	0.387	Ototoxicity:	0.423
Hematotoxicity:	0.234	Drug-induced Nephrotoxicity:	0.727
Genotoxicity:	0.941	RPMI-8226 Immunitoxicity:	0.007
A549 Cytotoxicity:	0.0	Hek293 Cytotoxicity:	0.01
BCF:	0.15 ? 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:	1.968 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.3 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	2.871 ? 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
NPO12631	Corylus avellana	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1007/s10616-014-9808-y]
NPO12631	Corylus avellana	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.stress.2021.100038]
NPO28679	Prunus mume	Species	Rosaceae	Eukaryota	flowers	n.a.	n.a.	PMID[12193020]
NPO7863	Dioscorea opposita	Species	Dioscoreaceae	Eukaryota	aerial parts	n.a.	n.a.	PMID[16124773]
NPO12631	Corylus avellana	Species	Betulaceae	Eukaryota	Shells; Leaves	n.a.	n.a.	PMID[18163585]
NPO1103	Dioscorea japonica	Species	Dioscoreaceae	Eukaryota	rhizomes	n.a.	n.a.	PMID[21353549]
NPO28679	Prunus mume	Species	Rosaceae	Eukaryota	fruits	n.a.	n.a.	PMID[24485782]
NPO24833	Dioscorea polystachya	Species	Dioscoreaceae	Eukaryota	n.a.	bark	n.a.	PMID[24689699]
NPO12631	Corylus avellana	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25420236]
NPO12631	Corylus avellana	Species	Betulaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[26606246]
NPO12631	Corylus avellana	Species	Betulaceae	Eukaryota	Green Leafy Covers	n.a.	n.a.	PMID[28520428]
NPO7863	Dioscorea opposita	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28679	Prunus mume	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1103	Dioscorea japonica	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12631	Corylus avellana	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12631	Corylus avellana	Species	Betulaceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO12631	Corylus avellana	Species	Betulaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO28679	Prunus mume	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1103	Dioscorea japonica	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO24833	Dioscorea polystachya	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1103	Dioscorea japonica	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28679	Prunus mume	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28679	Prunus mume	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7863	Dioscorea opposita	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO1103	Dioscorea japonica	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO24833	Dioscorea polystachya	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO28679	Prunus mume	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO7863	Dioscorea opposita	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO24833	Dioscorea polystachya	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12631	Corylus avellana	Species	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28679	Prunus mume	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7863	Dioscorea opposita	Species	Dioscoreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1103	Dioscorea japonica	Species	Dioscoreaceae	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	Organism Name	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
IZ	5
Activity	1

Activity Type	# Activity
Organism	6

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
NPT19	Organism	Escherichia coli	Escherichia coli	IZ	=	11.33	mm	PMID[28520428]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	IZ	=	6.67	mm	PMID[28520428]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IZ	=	11.33	mm	PMID[28520428]
NPT314	Organism	Bacillus cereus	Bacillus cereus	IZ	=	0.0	mm	PMID[28520428]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	29.0	%	PMID[7595594]

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
-	Rattus norvegicus	LD50	>	2000.0	mg/kg	ToxVal

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 NPC68743 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	20636
0.1-0.2	28074
0.2-0.3	1100
0.3-0.4	42
0.4-0.5	5
0.5-0.6	1
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	Natural Product ID
0.5556	Remote Similarity	NPC179624

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC68743 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6840
0.1-0.2	2258
0.2-0.3	51
0.3-0.4	1
0.4-0.5	0
0.5-0.6	0
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
		NPD

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