NPASS Compound

Natural Product: NPC605114

Natural Product ID	NPC605114
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	OFSAJYZMIPNPHE-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL137743
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 27 27 0 0 0 0 0 0 0 0999 V2000 -2.9229 -1.7169 1.3300 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1326 -0.6004 0.6876 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1527 -0.1330 1.2760 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5024 -0.0844 -0.5802 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.8239 0.9474 -1.2853 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4586 0.7284 -1.7764 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6290 0.3819 -0.9101 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0042 -0.9535 -0.7664 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0704 -1.2883 0.0789 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7538 -0.3291 0.7687 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8224 -0.6150 1.6222 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3759 0.9892 0.6206 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0842 1.9738 1.3345 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3313 1.3198 -0.2072 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2572 -2.2363 2.0296 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7417 -1.2727 1.9325 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3006 -2.3610 0.5223 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3813 -0.5661 -0.9773 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9263 1.9503 -0.7587 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4550 1.1416 -2.2186 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5077 0.0002 -2.6407 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1583 1.6961 -2.3154 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4987 -1.7519 -1.2879 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3748 -2.3249 0.2014 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7502 -0.3923 1.2745 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9641 1.9348 2.3465 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0623 2.3515 -0.3009 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 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 10 12 1 0 12 13 1 0 12 14 2 0 14 7 1 0 1 15 1 0 1 16 1 0 1 17 1 0 4 18 1 0 5 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 13 26 1 0 14 27 1 0 M END

Standard InCHIKey	OFSAJYZMIPNPHE-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C10H13NO3/c1-7(12)11-5-4-8-2-3-9(13)10(14)6-8/h2-3,6,13-14H,4-5H2,1H3,(H,11,12)
SMILES	CC(=O)NCCc1ccc(O)c(O)c1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	195.09	Volume:	199.781 ? Van der Waals volume.
Dense:	0.977	LogP:	-0.407 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.13 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.091 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	7.0
TPSA:	69.56 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	3.0	Rings:	1.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.624	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	1.863	Fsp³:	0.3
MCE-18:	7.0 ? 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:	1	PAINS Alert:	1
Colloidal aggregators:	0.224	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.009 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.114 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.021	Promiscuous compounds:	0.366

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.059	MDCK Permeability:	-4.546
Pgp-inhibitor:	0.003	Pgp-substrate:	0.997
PAMPA:	0.525 ? 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):	0.661
20% Bioavailability (F20%):	0.93	30% Bioavailability (F30%):	0.713
50% Bioavailability (F50%):	0.99

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.027	MRP1:	0.215
Plasma Protein Binding (PPB):	18.508%	Volume Distribution (VD):	-0.252
Fu:	78.499% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.764
OATP1B3 inhibitor:	0.245	BCRP inhibitor:	0.009
BSEP inhibitor:	0.024

ADMET: Metabolism

CYP1A2-inhibitor:	0.951	CYP1A2-substrate:	0.004
CYP2C19-inhibitor:	0.994	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.912	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.987	CYP2D6-substrate:	0.067
CYP3A4-inhibitor:	0.029	CYP3A4-substrate:	0.003
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.037
HLM stability:	0.707 ? 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):

14.683

Half-life (T1/2):

1.746

ADMET: Toxicity

hERG Blockers:	0.114	hERG Blockers (10um):	0.745
Human Hepatotoxicity (H-HT):	0.804	Drug-induced Liver Injury (DILI):	0.174
AMES Toxicity:	0.433	Rat Oral Acute Toxicity:	0.088
Maximum Recommended Daily Dose:	0.699	Skin Sensitization:	0.976
Carcinogencity:	0.301	Eye Corrosion:	0.007
Eye Irritation:	0.756	Respiratory Toxicity:	0.096
Drug-induced Neurotoxicity:	0.06	Ototoxicity:	0.771
Hematotoxicity:	0.326	Drug-induced Nephrotoxicity:	0.149
Genotoxicity:	0.979	RPMI-8226 Immunitoxicity:	0.012
A549 Cytotoxicity:	0.175	Hek293 Cytotoxicity:	0.067
BCF:	0.375 ? 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:	2.928 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.378 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.494 ? 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
NPO59032	Cryptotympana sp.	Genus	Cicadidae	Eukaryota	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

Activity Type	# Activity
Potency	28
AC50	5
IC50	3

Activity Type	# Activity
Individual protein	27
Cell line	2
Unchecked	1
Non-molecular	6

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT110	Individual protein	Cytochrome P450 2D6	Homo sapiens	AC50	n.a.	n.a.	n.a.	PubChem BioAssay data set
NPT150	Individual protein	Anthrax lethal factor	Bacillus anthracis	Potency	=	31622.8	nM	PubChem BioAssay data set
NPT208	Individual protein	Cytochrome P450 1A2	Homo sapiens	AC50	n.a.	n.a.	n.a.	PubChem BioAssay data set
NPT149	Individual protein	Endoplasmic reticulum-associated amyloid beta-peptide-binding protein	Homo sapiens	Potency	=	501.2	nM	PubChem BioAssay data set
NPT109	Individual protein	Cytochrome P450 3A4	Homo sapiens	AC50	n.a.	n.a.	n.a.	PubChem BioAssay data set
NPT211	Individual protein	Hypoxia-inducible factor 1 alpha	Homo sapiens	Potency	=	12589.3	nM	PubChem BioAssay data set
NPT149	Individual protein	Endoplasmic reticulum-associated amyloid beta-peptide-binding protein	Homo sapiens	Potency	=	7943.3	nM	PubChem BioAssay data set
NPT30	Individual protein	Cyclooxygenase-1	Homo sapiens	IC50	=	18900.0	nM	PMID[25442305]
NPT213	Individual protein	Cytochrome P450 2C19	Homo sapiens	AC50	n.a.	n.a.	n.a.	PubChem BioAssay data set
NPT212	Individual protein	Cytochrome P450 2C9	Homo sapiens	AC50	n.a.	n.a.	n.a.	PubChem BioAssay data set
NPT151	Individual protein	15-hydroxyprostaglandin dehydrogenase [NAD+]	Homo sapiens	Potency	=	39810.7	nM	PubChem BioAssay data set
NPT58	Individual protein	Bloom syndrome protein	Homo sapiens	Potency	=	1000.0	nM	PubChem BioAssay data set
NPT55	Individual protein	Putative fructose-1,6-bisphosphate aldolase	Giardia intestinalis	Potency	=	9976.3	nM	PubChem BioAssay data set
NPT483	Individual protein	Prelamin-A/C	Homo sapiens	Potency	=	5623.4	nM	PubChem BioAssay data set
NPT7	Individual protein	Thioredoxin reductase 1, cytoplasmic	Rattus norvegicus	Potency	n.a.	26679.5	nM	PubChem BioAssay data set
NPT94	Individual protein	Aldehyde dehydrogenase 1A1	Homo sapiens	Potency	=	28183.8	nM	PubChem BioAssay data set
NPT800	Individual protein	M-phase phosphoprotein 8	Homo sapiens	Potency	n.a.	100000.0	nM	PubChem BioAssay data set
NPT48	Individual protein	Lysine-specific demethylase 4D-like	Homo sapiens	Potency	=	17782.8	nM	PubChem BioAssay data set
NPT95	Individual protein	Muscarinic acetylcholine receptor M1	Rattus norvegicus	Potency	=	17782.8	nM	PubChem BioAssay data set
NPT51	Individual protein	Microtubule-associated protein tau	Homo sapiens	Potency	=	14125.4	nM	PubChem BioAssay data set
NPT794	Individual protein	Endonuclease 4	Escherichia coli K-12	Potency	=	25118.9	nM	PubChem BioAssay data set
NPT49	Individual protein	DNA-(apurinic or apyrimidinic site) lyase	Homo sapiens	Potency	n.a.	56234.1	nM	PubChem BioAssay data set
NPT5	Individual protein	Histone-lysine N-methyltransferase, H3 lysine-9 specific 3	Homo sapiens	Potency	n.a.	1995.3	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT319	Cell line	B16	Mus musculus	IC50	=	2060000.0	nM	PMID[1447731]
NPT319	Cell line	B16	Mus musculus	IC50	=	1220000.0	nM	PMID[1447731]
NPT28438	Unchecked	Unchecked	n.a.	Potency	=	14.1	nM	PubChem BioAssay data set
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Potency	=	10000.0	nM	PubChem BioAssay data set

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
-	Mus musculus	LD50	=	1.910308617	mg/kg	TOXRIC

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 NPC605114 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	20835
0.1-0.2	25127
0.2-0.3	3601
0.3-0.4	254
0.4-0.5	38
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
0.5676	Remote Similarity	NPC604260
0.5135	Remote Similarity	NPC228343
0.5135	Remote Similarity	NPC565062

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC605114 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3351
0.1-0.2	5514
0.2-0.3	249
0.3-0.4	23
0.4-0.5	11
0.5-0.6	2
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
0.5135	Remote Similarity	NPD3021	Approved
0.5135	Remote Similarity	NPD3022	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