NPASS Compound

Natural Product: NPC527427

Natural Product ID	NPC527427
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	ACETYL TRIBUTYL CITRATE
IUPAC Name	tributyl 2-acetoxypropane-1,2,3-tricarboxylate
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 -6.9113 -2.9238 0.4317 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4218 -1.8398 1.3289 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3601 -0.9604 0.7551 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1365 -1.7560 0.3889 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1637 -0.8601 -0.1505 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9201 -1.2595 -0.5897 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6266 -2.4803 -0.5106 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9063 -0.3406 -1.1496 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1893 -0.0007 -0.1462 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9181 -1.2052 0.3156 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5987 -2.0057 -0.6966 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5626 -1.6952 -1.9021 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3093 -3.1419 -0.3451 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9994 -3.9776 -1.2442 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0935 -3.2890 -1.9982 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1534 -2.7162 -1.0714 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1976 -2.0515 -1.9406 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5362 0.5248 0.9823 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1516 0.9842 2.0823 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6022 1.5271 3.2697 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3997 0.9997 2.2074 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0055 1.0808 -0.7201 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7257 0.8742 -1.7218 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0359 2.3744 -0.2066 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8344 3.3955 -0.7833 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7054 4.6972 -0.0678 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2730 5.2217 -0.0706 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3280 6.5475 0.6974 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3897 -3.0003 -0.5401 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0083 -2.8092 0.1912 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8104 -3.9013 0.9429 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0059 -2.2892 2.2702 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2916 -1.1966 1.6151 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0549 -0.2465 1.5511 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7719 -0.3965 -0.1069 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4241 -2.5115 -0.3599 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7695 -2.2705 1.2887 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4701 -0.6561 -2.1042 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3812 0.6630 -1.3762 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6445 -0.9341 1.1052 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1642 -1.8517 0.8482 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4258 -4.8117 -0.6421 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3073 -4.4148 -2.0073 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5916 -3.9340 -2.7349 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6559 -2.4368 -2.5521 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6405 -3.5543 -0.5295 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7226 -1.9755 -0.3686 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0792 -2.3612 -2.9934 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0827 -0.9356 -1.8418 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2259 -2.3537 -1.6422 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4517 2.6339 3.2354 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6755 1.3301 3.1856 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1441 1.0619 4.1665 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4561 3.5351 -1.8169 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8936 3.1269 -0.8331 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3145 5.4701 -0.5786 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9991 4.6314 1.0017 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4241 4.5401 0.4224 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0827 5.4534 -1.0938 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6941 6.9136 0.9034 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8235 7.3316 0.0866 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9263 6.4263 1.6272 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 1 0 5 6 1 0 6 7 2 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 11 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 9 18 1 0 18 19 1 0 19 20 1 0 19 21 2 0 9 22 1 0 22 23 2 0 22 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 1 29 1 0 1 30 1 0 1 31 1 0 2 32 1 0 2 33 1 0 3 34 1 0 3 35 1 0 4 36 1 0 4 37 1 0 8 38 1 0 8 39 1 0 10 40 1 0 10 41 1 0 14 42 1 0 14 43 1 0 15 44 1 0 15 45 1 0 16 46 1 0 16 47 1 0 17 48 1 0 17 49 1 0 17 50 1 0 20 51 1 0 20 52 1 0 20 53 1 0 25 54 1 0 25 55 1 0 26 56 1 0 26 57 1 0 27 58 1 0 27 59 1 0 28 60 1 0 28 61 1 0 28 62 1 0 M END

Standard InCHIKey	QZCLKYGREBVARF-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C20H34O8/c1-5-8-11-25-17(22)14-20(28-16(4)21,19(24)27-13-10-7-3)15-18(23)26-12-9-6-2/h5-15H2,1-4H3
SMILES	CCCCOC(=O)CC(CC(=O)OCCCC)(OC(C)=O)C(=O)OCCCC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	402.23	Volume:	414.252 ? Van der Waals volume.
Dense:	0.971	LogP:	4.543 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.518 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.273 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	19.0	Rigid Bonds:	4.0
TPSA:	105.2 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	0.0	Rings:	0.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.234	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.693	Fsp³:	0.8
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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.016	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.005 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.035 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.977	Promiscuous compounds:	0.002

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.839	MDCK Permeability:	-4.635
Pgp-inhibitor:	0.007	Pgp-substrate:	0.036
PAMPA:	0.437 ? 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):	0.21
20% Bioavailability (F20%):	0.989	30% Bioavailability (F30%):	0.994
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.057	MRP1:	0.941
Plasma Protein Binding (PPB):	95.017%	Volume Distribution (VD):	0.248
Fu:	6.834% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.939
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.0
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.008	CYP1A2-substrate:	0.998
CYP2C19-inhibitor:	0.341	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.021	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.997	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.002	CYP2C8-inhibitor:	0.038
HLM stability:	0.996 ? 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):

6.28

Half-life (T1/2):

0.233

ADMET: Toxicity

hERG Blockers:	0.097	hERG Blockers (10um):	0.527
Human Hepatotoxicity (H-HT):	0.117	Drug-induced Liver Injury (DILI):	0.385
AMES Toxicity:	0.039	Rat Oral Acute Toxicity:	0.126
Maximum Recommended Daily Dose:	0.108	Skin Sensitization:	0.402
Carcinogencity:	0.255	Eye Corrosion:	0.026
Eye Irritation:	0.587	Respiratory Toxicity:	0.031
Drug-induced Neurotoxicity:	0.172	Ototoxicity:	0.079
Hematotoxicity:	0.034	Drug-induced Nephrotoxicity:	0.286
Genotoxicity:	0.093	RPMI-8226 Immunitoxicity:	0.018
A549 Cytotoxicity:	0.001	Hek293 Cytotoxicity:	0.014
BCF:	1.32 ? 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:	4.016 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.23 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.07 ? 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
NPO8159	Digenea simplex	Species	Rhodomelaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31117523]
NPO8159	Digenea simplex	Species	Rhodomelaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36536224]
NPO64536	Barleria albostellata	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37446958]
NPO50112	Onosma malatyana	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39205636]
NPO8159	Digenea simplex	Species	Rhodomelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8159	Digenea simplex	Species	Rhodomelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8159	Digenea simplex	Species	Rhodomelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8159	Digenea simplex	Species	Rhodomelaceae	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
NPO50112	Onosma malatyana	Oil	Roots	1.82	n.a.	n.a.	%	PMID[39205636]
NPO64536	Barleria albostellata	n.a.	Stems	1.05	n.a.	n.a.	%	PMID[37446958]
NPO8159	Digenea simplex	Chloroform extract	n.a.	0.73	n.a.	n.a.	%	PMID[36536224]

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
-	Felis catus	LOEL	=	5.0	mg/kg-day	ToxVal
-	Felis catus	NOEL	<	5.0	mg/kg-day	ToxVal
-	Felis catus	LD50	>	50000.0	mg/kg	ToxVal
-	Rattus norvegicus	NOAEL	=	300.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOAEL	=	100.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOAEL	=	1000.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOAEL	>=	1000.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOEL	~	100.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOAEL	~	300.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOEL	~	300.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOAEL	<=	1000.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOAEL	~	2000.0	mg/kg-day	ToxVal
-	Rattus norvegicus	LOEL	=	1000.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOEL	=	300.0	mg/kg-day	ToxVal
-	Rattus norvegicus	LOAEL	=	1000.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOAEL	>	1000.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOEL	=	250.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOAEL	>=	100.0	mg/kg-day	ToxVal
-	Rattus norvegicus	LD50	>	30.0	mL/kg bw	ToxVal
-	Rattus norvegicus	LD50	>	31500.0	mg/kg	ToxVal
-	Mus musculus	LD50	=	2.002688629	mg/kg	TOXRIC
-	Mus musculus	NOEL	=	250.0	mg/kg-day	ToxVal
-	Oryctolagus cuniculus	LD50	>	1000.0	mg/kg	ToxVal
-	Homo sapiens	DNEL systemic	=	7.05	mg/m3	ToxVal
-	Homo sapiens	DNEL systemic	=	7.04	mg/m3	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 NPC527427 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	28291
0.1-0.2	20898
0.2-0.3	614
0.3-0.4	32
0.4-0.5	21
0.5-0.6	3
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
0.5333	Remote Similarity	NPC166804
0.5172	Remote Similarity	NPC3693
0.5172	Remote Similarity	NPC476549

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC527427 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7211
0.1-0.2	1874
0.2-0.3	60
0.3-0.4	3
0.4-0.5	1
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	Drug ID	Developmental Stage
0.5161	Remote Similarity	NPD900	Pre-clinical

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