NPASS Compound

Natural Product: NPC118459

Natural Product ID	NPC118459
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Norvaline
IUPAC Name	(2S)-2-azaniumylpentanoate
Synonyms	2-Amino-Pentanoic Acid; L-Norvaline
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL55612
PubChem CID	6950514 65098
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000347] Amino acids and derivatives [CHEMONTID:0000060] Alpha amino acids and derivatives [CHEMONTID:0002404] Alpha amino acids [CHEMONTID:0004146] L-alpha-amino acids

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

Chemical Representations

Standard InCHIKey	SNDPXSYFESPGGJ-BYPYZUCNSA-N
Standard InCHI	InChI=1S/C5H11NO2/c1-2-3-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8)/t4-/m0/s1
SMILES	CCC[C@@H](C(=O)O)N

Calculated Properties

Physi-Chem Properties

Molecular Weight:	117.08	Volume:	120.977 ? Van der Waals volume.
Dense:	0.968	LogP:	-1.824 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.292 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	0.153 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	1.0
TPSA:	63.32 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	3.0	Rings:	0.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.555	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.391	Fsp³:	0.8
MCE-18:	2.0 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.601	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.014 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.003 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.899	Promiscuous compounds:	0.96

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.739	MDCK Permeability:	-4.418
Pgp-inhibitor:	0.0	Pgp-substrate:	0.054
PAMPA:	0.976 ? 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):	0.0
20% Bioavailability (F20%):	0.001	30% Bioavailability (F30%):	0.0
50% Bioavailability (F50%):	0.025

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.01	MRP1:	0.668
Plasma Protein Binding (PPB):	24.8%	Volume Distribution (VD):	-0.087
Fu:	75.04% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.676
OATP1B3 inhibitor:	0.904	BCRP inhibitor:	0.0
BSEP inhibitor:	0.02

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.024	CYP2C9-substrate:	0.002
CYP2D6-inhibitor:	0.997	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.013
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.269
HLM stability:	0.001 ? 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):

7.332

Half-life (T1/2):

1.061

ADMET: Toxicity

hERG Blockers:	0.066	hERG Blockers (10um):	0.247
Human Hepatotoxicity (H-HT):	0.536	Drug-induced Liver Injury (DILI):	0.076
AMES Toxicity:	0.407	Rat Oral Acute Toxicity:	0.458
Maximum Recommended Daily Dose:	0.08	Skin Sensitization:	0.785
Carcinogencity:	0.32	Eye Corrosion:	0.909
Eye Irritation:	0.962	Respiratory Toxicity:	0.657
Drug-induced Neurotoxicity:	0.398	Ototoxicity:	0.172
Hematotoxicity:	0.227	Drug-induced Nephrotoxicity:	0.664
Genotoxicity:	0.155	RPMI-8226 Immunitoxicity:	0.063
A549 Cytotoxicity:	0.022	Hek293 Cytotoxicity:	0.033
BCF:	0.257 ? 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:	2.763 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.823 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.172 ? 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
NPO2567	Serratia marcescens	Species	Yersiniaceae	Bacteria	n.a.	n.a.	n.a.	PMID[14325279]
NPO2567	Serratia marcescens	Species	Yersiniaceae	Bacteria	n.a.	n.a.	n.a.	PMID[15853884]
NPO2567	Serratia marcescens	Species	Yersiniaceae	Bacteria	n.a.	n.a.	n.a.	PMID[18313305]
NPO2567	Serratia marcescens	Species	Yersiniaceae	Bacteria	n.a.	n.a.	n.a.	PMID[783153]
NPO2567	Serratia marcescens	Species	Yersiniaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2567	Serratia marcescens	Species	Yersiniaceae	Bacteria	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
Ki	1
pKi	1

Activity Type	# Activity
Individual protein	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1006	Individual protein	Proton-coupled amino acid transporter 1	Homo sapiens	Ki	=	46000000.0	nM	PMID[21955456]
NPT1006	Individual protein	Proton-coupled amino acid transporter 1	Homo sapiens	pKi	=	-1.66	mM	PMID[21955456]

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 NPC118459 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	40310
0.1-0.2	8398
0.2-0.3	821
0.3-0.4	195
0.4-0.5	62
0.5-0.6	29
0.6-0.7	13
0.7-0.8	5
0.8-0.85	0
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	NPC327698
1.0	High Similarity	NPC53449
0.7778	Intermediate Similarity	NPC63621
0.7778	Intermediate Similarity	NPC326992
0.7778	Intermediate Similarity	NPC121517
0.7778	Intermediate Similarity	NPC168375
0.7778	Intermediate Similarity	NPC600066
0.7619	Intermediate Similarity	NPC167986
0.7619	Intermediate Similarity	NPC291186
0.7059	Intermediate Similarity	NPC116709
0.7059	Intermediate Similarity	NPC21290
0.7059	Intermediate Similarity	NPC272614
0.6667	Remote Similarity	NPC245027
0.6667	Remote Similarity	NPC162620
0.6667	Remote Similarity	NPC62045
0.6667	Remote Similarity	NPC601942
0.625	Remote Similarity	NPC102815
0.619	Remote Similarity	NPC329263
0.619	Remote Similarity	NPC309658
0.619	Remote Similarity	NPC604272
0.619	Remote Similarity	NPC607953
0.6087	Remote Similarity	NPC140872
0.6087	Remote Similarity	NPC93081
0.6	Remote Similarity	NPC132307
0.6	Remote Similarity	NPC126925
0.5909	Remote Similarity	NPC84636
0.5909	Remote Similarity	NPC226027
0.5909	Remote Similarity	NPC174246
0.5909	Remote Similarity	NPC43204
0.5833	Remote Similarity	NPC608987
0.5652	Remote Similarity	NPC49952
0.5652	Remote Similarity	NPC153370
0.5652	Remote Similarity	NPC34908
0.5652	Remote Similarity	NPC136476
0.56	Remote Similarity	NPC279661
0.56	Remote Similarity	NPC183845
0.56	Remote Similarity	NPC324825
0.56	Remote Similarity	NPC112890
0.56	Remote Similarity	NPC316231
0.55	Remote Similarity	NPC237525
0.55	Remote Similarity	NPC326212
0.5455	Remote Similarity	NPC270805
0.5455	Remote Similarity	NPC93888
0.5417	Remote Similarity	NPC137958
0.5417	Remote Similarity	NPC273330
0.5417	Remote Similarity	NPC600338
0.5385	Remote Similarity	NPC190184
0.5385	Remote Similarity	NPC197087
0.5263	Remote Similarity	NPC9294
0.5238	Remote Similarity	NPC198301
0.52	Remote Similarity	NPC322532
0.52	Remote Similarity	NPC50047
0.5185	Remote Similarity	NPC602488
0.5172	Remote Similarity	NPC38463

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC118459 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6478
0.1-0.2	2241
0.2-0.3	306
0.3-0.4	77
0.4-0.5	24
0.5-0.6	8
0.6-0.7	4
0.7-0.8	5
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
0.7619	Intermediate Similarity	NPD8804	Phase 4
0.7619	Intermediate Similarity	NPD8805	Approved
0.7619	Intermediate Similarity	NPD9016	Phase 1
0.7059	Intermediate Similarity	NPD8210	Phase 3
0.7059	Intermediate Similarity	NPD8211	Approved
0.6667	Remote Similarity	NPD9018	Phase 3
0.6522	Remote Similarity	NPD9021	Pre-clinical
0.6087	Remote Similarity	NPD8809	Phase 3
0.6	Remote Similarity	NPD8798	Phase 2
0.5909	Remote Similarity	NPD9017	Phase 2
0.5652	Remote Similarity	NPD8614	Pre-clinical
0.56	Remote Similarity	NPD9044	Phase 4
0.5455	Remote Similarity	NPD8624	Phase 2
0.5455	Remote Similarity	NPD8801	Phase 4
0.5417	Remote Similarity	NPD8872	Phase 3
0.5385	Remote Similarity	NPD8785	Phase 4
0.52	Remote Similarity	NPD8871	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