NPASS Compound

Natural Product: NPC543409

Natural Product ID	NPC543409
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3-hydroxy-4-(1H-indol-3-yl)butan-2-one
IUPAC Name	3-hydroxy-4-(1~{H}-indol-3-yl)butan-2-one
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 28 29 0 0 0 0 0 0 0 0999 V2000 -4.3799 0.5041 -0.0045 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0819 0.7138 0.7207 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1920 1.0760 1.8936 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7614 0.4993 0.0691 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0054 0.0918 -1.2399 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0216 -0.5737 0.8310 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3099 -0.8585 0.2541 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6216 -1.9591 -0.5095 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9234 -1.8573 -0.8434 N 0 0 0 0 0 0 0 0 0 0 0 0 2.4401 -0.7386 -0.3209 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7112 -0.2042 -0.3824 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0206 0.9833 0.2451 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0086 1.6195 0.9394 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7356 1.1072 1.0150 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4449 -0.0795 0.3822 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2186 0.2517 -1.0720 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0177 1.4312 0.0371 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9374 -0.2764 0.5469 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1575 1.4327 -0.0016 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0722 -0.8933 -1.2825 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9623 -0.3424 1.9139 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6635 -1.4942 0.7702 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0235 -2.7885 -0.8161 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4514 -2.5425 -1.4213 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5312 -0.6819 -0.9214 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0379 1.3947 0.1863 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2724 2.5587 1.4301 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9861 1.6260 1.5585 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 4 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 7 1 0 15 10 1 0 1 16 1 0 1 17 1 0 1 18 1 0 4 19 1 0 5 20 1 0 6 21 1 0 6 22 1 0 8 23 1 0 9 24 1 0 11 25 1 0 12 26 1 0 13 27 1 0 14 28 1 0 M END

Standard InCHIKey	HRSIDIKGNJOTMN-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C12H13NO2/c1-8(14)12(15)6-9-7-13-11-5-3-2-4-10(9)11/h2-5,7,12-13,15H,6H2,1H3
SMILES	CC(=O)C(O)CC1=CNC2=CC=CC=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	203.09	Volume:	214.39 ? Van der Waals volume.
Dense:	0.947	LogP:	1.822 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.716 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.322 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	11.0
TPSA:	53.09 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.797	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.577	Fsp³:	0.25
MCE-18:	22.0 ? 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:	0.169	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.056 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.096 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.176	Promiscuous compounds:	0.274

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.129	MDCK Permeability:	-4.63
Pgp-inhibitor:	0.013	Pgp-substrate:	0.482
PAMPA:	0.62 ? 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):	0.002
20% Bioavailability (F20%):	0.017	30% Bioavailability (F30%):	0.11
50% Bioavailability (F50%):	0.872

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.445	MRP1:	0.621
Plasma Protein Binding (PPB):	65.997%	Volume Distribution (VD):	0.095
Fu:	34.779% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.629
OATP1B3 inhibitor:	0.979	BCRP inhibitor:	0.228
BSEP inhibitor:	0.584

ADMET: Metabolism

CYP1A2-inhibitor:	0.007	CYP1A2-substrate:	0.641
CYP2C19-inhibitor:	0.004	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.031	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.263	CYP2D6-substrate:	0.049
CYP3A4-inhibitor:	0.103	CYP3A4-substrate:	0.003
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.538
HLM stability:	0.96 ? 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):

10.199

Half-life (T1/2):

1.621

ADMET: Toxicity

hERG Blockers:	0.078	hERG Blockers (10um):	0.411
Human Hepatotoxicity (H-HT):	0.531	Drug-induced Liver Injury (DILI):	0.224
AMES Toxicity:	0.491	Rat Oral Acute Toxicity:	0.361
Maximum Recommended Daily Dose:	0.527	Skin Sensitization:	0.126
Carcinogencity:	0.514	Eye Corrosion:	0.015
Eye Irritation:	0.828	Respiratory Toxicity:	0.635
Drug-induced Neurotoxicity:	0.529	Ototoxicity:	0.616
Hematotoxicity:	0.302	Drug-induced Nephrotoxicity:	0.354
Genotoxicity:	0.734	RPMI-8226 Immunitoxicity:	0.023
A549 Cytotoxicity:	0.04	Hek293 Cytotoxicity:	0.095
BCF:	0.303 ? 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:	2.922 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.272 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.461 ? 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
NPO62724	Actinopolymorpha rutilus	Genus	Actinopolymorphaceae	Bacteria	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

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 NPC543409 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	21154
0.1-0.2	27045
0.2-0.3	1088
0.3-0.4	412
0.4-0.5	101
0.5-0.6	40
0.6-0.7	4
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8409	Intermediate Similarity	NPC480551
0.7872	Intermediate Similarity	NPC480550
0.6364	Remote Similarity	NPC230869
0.6275	Remote Similarity	NPC469358
0.619	Remote Similarity	NPC601214
0.6	Remote Similarity	NPC279081
0.587	Remote Similarity	NPC29886
0.587	Remote Similarity	NPC72435
0.5849	Remote Similarity	NPC480549
0.5833	Remote Similarity	NPC310665
0.58	Remote Similarity	NPC315555
0.5778	Remote Similarity	NPC96102
0.5769	Remote Similarity	NPC609424
0.566	Remote Similarity	NPC200214
0.5614	Remote Similarity	NPC606619
0.5614	Remote Similarity	NPC610347
0.56	Remote Similarity	NPC267343
0.551	Remote Similarity	NPC605863
0.549	Remote Similarity	NPC55772
0.549	Remote Similarity	NPC600736
0.5424	Remote Similarity	NPC603162
0.5417	Remote Similarity	NPC84911
0.5417	Remote Similarity	NPC154339
0.54	Remote Similarity	NPC603879
0.5385	Remote Similarity	NPC190296
0.537	Remote Similarity	NPC608269
0.5333	Remote Similarity	NPC102423
0.5333	Remote Similarity	NPC300149
0.5333	Remote Similarity	NPC42372
0.5306	Remote Similarity	NPC73767
0.5294	Remote Similarity	NPC78020
0.5283	Remote Similarity	NPC489200
0.5283	Remote Similarity	NPC480318
0.5263	Remote Similarity	NPC480548
0.5263	Remote Similarity	NPC609408
0.5192	Remote Similarity	NPC59269
0.5179	Remote Similarity	NPC602670
0.5094	Remote Similarity	NPC149155
0.5094	Remote Similarity	NPC203468
0.5094	Remote Similarity	NPC110500
0.5094	Remote Similarity	NPC605329
0.5085	Remote Similarity	NPC11126
0.5085	Remote Similarity	NPC71037
0.5085	Remote Similarity	NPC605381
0.5079	Remote Similarity	NPC481141
0.5079	Remote Similarity	NPC606618

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC543409 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3950
0.1-0.2	5000
0.2-0.3	143
0.3-0.4	44
0.4-0.5	9
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
0.5778	Remote Similarity	NPD198	Clinical (unspecified phase)
0.551	Remote Similarity	NPD786	Pre-clinical
0.5283	Remote Similarity	NPD749	Clinical (unspecified phase)
0.5094	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