NPASS Compound

Natural Product: NPC315491

Natural Product ID	NPC315491
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2-Amino-3-(5-Hydroxy-1H-Indol-3-Yl)Propanoic Acid
IUPAC Name	2-amino-3-(5-hydroxy-1H-indol-3-yl)propanoic acid
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL162789
PubChem CID	144 25243949
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000211] Indoles and derivatives [CHEMONTID:0000183] Tryptamines and derivatives [CHEMONTID:0001637] Serotonins

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 28 29 0 0 0 0 0 0 0 0999 V2000 -1.3985 1.5438 0.6064 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0720 1.1240 -0.5502 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2818 1.9412 -1.4745 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5104 -0.2698 -0.6270 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3436 -1.1850 -0.8682 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2790 -1.1636 0.1257 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2181 -1.9864 1.2542 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8613 -1.6474 1.9429 N 0 0 0 0 0 0 0 0 0 0 0 0 1.5396 -0.6353 1.3381 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8040 -0.3359 0.1820 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3194 0.6758 -0.6271 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4758 1.3385 -0.3092 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8985 2.3339 -1.1941 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1716 1.0249 0.8270 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6941 0.0269 1.6547 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4321 -0.4273 -1.7830 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.4748 2.5090 0.9205 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0983 -0.6014 0.2599 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8452 -0.9362 -1.8584 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7445 -2.2286 -1.0587 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9401 -2.7603 1.5036 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1661 -2.1002 2.8537 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7560 0.9094 -1.5243 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1742 3.2351 -0.8304 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0947 1.5592 1.0715 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2495 -0.2161 2.5555 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8410 -0.2750 -2.6246 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7257 -1.4530 -1.7658 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 12 14 1 0 14 15 2 0 4 16 1 0 10 6 1 0 15 9 1 0 1 17 1 0 4 18 1 0 5 19 1 0 5 20 1 0 7 21 1 0 8 22 1 0 11 23 1 0 13 24 1 0 14 25 1 0 15 26 1 0 16 27 1 0 16 28 1 0 M END

Standard InCHIKey	LDCYZAJDBXYCGN-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C11H12N2O3/c12-9(11(15)16)3-6-5-13-10-2-1-7(14)4-8(6)10/h1-2,4-5,9,13-14H,3,12H2,(H,15,16)
SMILES	OC(=O)C(Cc1c[nH]c2c1cc(O)cc2)N

Calculated Properties

Physi-Chem Properties

Molecular Weight:	220.08	Volume:	216.881 ? Van der Waals volume.
Dense:	1.015	LogP:	-2.246 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.089 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.695 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	11.0
TPSA:	99.34 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	5.0	Rings:	2.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.615	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.587	Fsp³:	0.182
MCE-18:	24.0 ? 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:	0.365	Fluc inhibitor:	0.137 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.229 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.075 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.04	Promiscuous compounds:	0.825

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.944	MDCK Permeability:	-4.24
Pgp-inhibitor:	0.0	Pgp-substrate:	0.487
PAMPA:	0.957 ? 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%):	0.0	30% Bioavailability (F30%):	0.0
50% Bioavailability (F50%):	0.038

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.016	MRP1:	0.626
Plasma Protein Binding (PPB):	30.545%	Volume Distribution (VD):	-0.113
Fu:	69.708% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.862
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.0
BSEP inhibitor:	0.217

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.003
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.983	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.999	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.01
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):

13.434

Half-life (T1/2):

1.456

ADMET: Toxicity

hERG Blockers:	0.097	hERG Blockers (10um):	0.249
Human Hepatotoxicity (H-HT):	0.5	Drug-induced Liver Injury (DILI):	0.041
AMES Toxicity:	0.504	Rat Oral Acute Toxicity:	0.574
Maximum Recommended Daily Dose:	0.65	Skin Sensitization:	0.101
Carcinogencity:	0.374	Eye Corrosion:	0.004
Eye Irritation:	0.588	Respiratory Toxicity:	0.623
Drug-induced Neurotoxicity:	0.645	Ototoxicity:	0.396
Hematotoxicity:	0.143	Drug-induced Nephrotoxicity:	0.267
Genotoxicity:	0.86	RPMI-8226 Immunitoxicity:	0.04
A549 Cytotoxicity:	0.057	Hek293 Cytotoxicity:	0.161
BCF:	0.312 ? 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:	2.802 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.046 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.263 ? 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
NPO18994	Mucuna pruriens	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18994	Mucuna pruriens	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO18994	Mucuna pruriens	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18994	Mucuna pruriens	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO18994	Mucuna pruriens	Species	Fabaceae	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
Inhibition	2
BP	7
IC50	2

Activity Type	# Activity
Organism	9
Individual protein	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	9.26	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	-5.11	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	IC50	>	20000.0	nM	DOI[10.6019/CHEMBL4651402]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	IC50	>	19952.62	nM	DOI[10.6019/CHEMBL4651402]
NPT1403	Organism	Felis catus	Felis catus	BP	=	162.0	mmHg	PMID[7097726]
NPT1403	Organism	Felis catus	Felis catus	BP	=	-24.0	mmHg	PMID[7097726]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	BP	=	-9.0	mmHg	PMID[7097726]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	BP	=	-5.0	mmHg	PMID[7097726]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	BP	=	0.0	mmHg	PMID[7097726]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	BP	=	6.0	mmHg	PMID[7097726]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	BP	=	-1.0	mmHg	PMID[7097726]

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 NPC315491 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	30290
0.1-0.2	18296
0.2-0.3	1101
0.3-0.4	125
0.4-0.5	20
0.5-0.6	16
0.6-0.7	8
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC45459
0.7059	Intermediate Similarity	NPC88008
0.6667	Remote Similarity	NPC149155
0.6667	Remote Similarity	NPC203468
0.6667	Remote Similarity	NPC110500
0.6538	Remote Similarity	NPC480321
0.6415	Remote Similarity	NPC480324
0.6415	Remote Similarity	NPC480325
0.6327	Remote Similarity	NPC220765
0.6154	Remote Similarity	NPC213308
0.5849	Remote Similarity	NPC204717
0.5818	Remote Similarity	NPC480320
0.5818	Remote Similarity	NPC480322
0.5741	Remote Similarity	NPC32771
0.5714	Remote Similarity	NPC480326
0.5625	Remote Similarity	NPC156704
0.5614	Remote Similarity	NPC314002
0.56	Remote Similarity	NPC276657
0.5556	Remote Similarity	NPC171171
0.5294	Remote Similarity	NPC171787
0.5263	Remote Similarity	NPC248041
0.5263	Remote Similarity	NPC480323
0.5185	Remote Similarity	NPC219087
0.5094	Remote Similarity	NPC74360
0.5091	Remote Similarity	NPC611528
0.5079	Remote Similarity	NPC476098

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC315491 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4803
0.1-0.2	4061
0.2-0.3	253
0.3-0.4	24
0.4-0.5	7
0.5-0.6	0
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	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD484	Phase 4
0.6667	Remote Similarity	NPD482	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