NPASS Compound

Natural Product: NPC599885

Natural Product ID	NPC599885
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	DXGLGDHPHMLXJC-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1625
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 29 30 0 0 0 0 0 0 0 0999 V2000 -5.3188 0.3443 -0.9742 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0412 0.3534 -1.5002 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8345 0.2316 -0.8620 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6416 0.2661 -1.5714 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4205 0.1438 -0.9356 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3235 -0.0193 0.4263 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9316 -0.1071 1.1165 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8873 0.0220 2.4092 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2408 -0.3180 0.5875 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5350 -1.0260 -0.5451 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8332 -1.1586 -1.0285 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8836 -0.5690 -0.3651 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6048 0.1395 0.7678 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3387 0.2645 1.2312 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5249 -0.0509 1.1191 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4311 -0.2160 2.5104 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7605 0.0701 0.5076 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3560 0.0982 0.0824 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0190 -0.3011 -1.5864 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7199 1.3926 -1.0697 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6920 0.3934 -2.6503 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4666 0.2120 -1.5807 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7616 -1.5359 -1.0922 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0691 -1.7165 -1.9236 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8971 -0.6847 -0.7612 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4575 0.5955 1.2740 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1474 0.8374 2.1389 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3117 0.5637 3.1301 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6591 0.0332 1.1453 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 7 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 6 15 1 0 15 16 1 0 15 17 2 0 17 3 1 0 14 9 1 0 1 18 1 0 1 19 1 0 1 20 1 0 4 21 1 0 5 22 1 0 10 23 1 0 11 24 1 0 12 25 1 0 13 26 1 0 14 27 1 0 16 28 1 0 17 29 1 0 M END

Standard InCHIKey	DXGLGDHPHMLXJC-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C14H12O3/c1-17-11-7-8-12(13(15)9-11)14(16)10-5-3-2-4-6-10/h2-9,15H,1H3
SMILES	COc1ccc(C(=O)c2ccccc2)c(O)c1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	228.08	Volume:	241.503 ? Van der Waals volume.
Dense:	0.944	LogP:	3.515 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.42 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.86 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	13.0
TPSA:	46.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	1.0	Rings:	2.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.821	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	1.554	Fsp³:	0.071
MCE-18:	11.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.106	Fluc inhibitor:	0.529 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.13 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.575 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.989	Promiscuous compounds:	0.372

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.864	MDCK Permeability:	-4.718
Pgp-inhibitor:	0.956	Pgp-substrate:	0.005
PAMPA:	0.026 ? 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):	0.013
20% Bioavailability (F20%):	0.014	30% Bioavailability (F30%):	0.39
50% Bioavailability (F50%):	0.47

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.091	MRP1:	0.083
Plasma Protein Binding (PPB):	97.806%	Volume Distribution (VD):	-0.186
Fu:	1.605% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.632
BSEP inhibitor:	0.974

ADMET: Metabolism

CYP1A2-inhibitor:	0.955	CYP1A2-substrate:	0.944
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.153
CYP2C9-inhibitor:	0.811	CYP2C9-substrate:	0.412
CYP2D6-inhibitor:	0.522	CYP2D6-substrate:	0.019
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.015
CYP2B6-substrate:	0.002	CYP2C8-inhibitor:	0.992
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):

6.489

Half-life (T1/2):

1.104

ADMET: Toxicity

hERG Blockers:	0.17	hERG Blockers (10um):	0.464
Human Hepatotoxicity (H-HT):	0.384	Drug-induced Liver Injury (DILI):	0.661
AMES Toxicity:	0.495	Rat Oral Acute Toxicity:	0.175
Maximum Recommended Daily Dose:	0.41	Skin Sensitization:	0.491
Carcinogencity:	0.375	Eye Corrosion:	0.031
Eye Irritation:	0.983	Respiratory Toxicity:	0.783
Drug-induced Neurotoxicity:	0.427	Ototoxicity:	0.207
Hematotoxicity:	0.257	Drug-induced Nephrotoxicity:	0.678
Genotoxicity:	0.259	RPMI-8226 Immunitoxicity:	0.108
A549 Cytotoxicity:	0.222	Hek293 Cytotoxicity:	0.354
BCF:	1.342 ? 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:	4.197 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.992 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.452 ? 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
NPO46900	Streptomyces aureus HP-S-01	Genus	Streptomycetaceae	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

Activity Type	# Activity
Potency	42
AC50	75
Inhibition	8
IC50	4
Hit score	1
SPF	1
Activity	1
Ratio	1
Inhibition index	1
%max	1
Hepatotoxicity	3

Activity Type	# Activity
Individual protein	107
Cell line	2
Single protein	2
Unchecked	8
Organism	12
Protein complex	2
Unknown	2
Phenotype	3

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT152	Individual protein	Nuclear factor erythroid 2-related factor 2	Homo sapiens	Potency	n.a.	74978.0	nM	PubChem BioAssay data set
NPT208	Individual protein	Cytochrome P450 1A2	Homo sapiens	AC50	=	1584.89	nM	PubChem BioAssay data set
NPT1410	Individual protein	GABA receptor alpha-1 subunit	Rattus norvegicus	AC50	>	30000.0	nM	PMID[37468498]
NPT1163	Individual protein	Glutamate (NMDA) receptor subunit zeta 1	Rattus norvegicus	AC50	>	30000.0	nM	PMID[37468498]
NPT108	Individual protein	Estrogen receptor alpha	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT110	Individual protein	Cytochrome P450 2D6	Homo sapiens	Potency	=	12589.3	nM	PubChem BioAssay data set
NPT291	Individual protein	Serotonin 2b (5-HT2b) receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT153	Individual protein	Androgen Receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT216	Individual protein	Adenosine A1 receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT154	Individual protein	Mothers against decapentaplegic homolog 3	Homo sapiens	Potency	n.a.	3981.1	nM	PubChem BioAssay data set
NPT243	Individual protein	Dopamine D2 receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT244	Individual protein	Dopamine D3 receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT110	Individual protein	Cytochrome P450 2D6	Homo sapiens	AC50	=	12589.25	nM	PubChem BioAssay data set
NPT1788	Individual protein	Alpha-1a adrenergic receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT263	Individual protein	Muscarinic acetylcholine receptor M2	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT204	Individual protein	Acetylcholinesterase	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT2761	Individual protein	Phosphodiesterase 4A	Homo sapiens	AC50	=	18140.1	nM	PMID[37468498]
NPT262	Individual protein	Muscarinic acetylcholine receptor M1	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT224	Individual protein	Alpha-2c adrenergic receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT228	Individual protein	Norepinephrine transporter	Homo sapiens	AC50	=	11580.0	nM	PMID[37468498]
NPT152	Individual protein	Nuclear factor erythroid 2-related factor 2	Homo sapiens	Potency	n.a.	27306.0	nM	PubChem BioAssay data set
NPT232	Individual protein	Cannabinoid CB1 receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT108	Individual protein	Estrogen receptor alpha	Homo sapiens	Potency	n.a.	31622.8	nM	PubChem BioAssay data set
NPT199	Individual protein	DNA polymerase kappa	Homo sapiens	Potency	n.a.	15848.9	nM	PubChem BioAssay data set
NPT242	Individual protein	Dopamine D1 receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT213	Individual protein	Cytochrome P450 2C19	Homo sapiens	Potency	=	398.1	nM	PubChem BioAssay data set
NPT282	Individual protein	MAP kinase ERK2	Homo sapiens	Potency	=	31622.8	nM	PubChem BioAssay data set
NPT30	Individual protein	Cyclooxygenase-1	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT151	Individual protein	15-hydroxyprostaglandin dehydrogenase [NAD+]	Homo sapiens	Potency	=	15848.9	nM	PubChem BioAssay data set
NPT109	Individual protein	Cytochrome P450 3A4	Homo sapiens	AC50	n.a.	n.a.	n.a.	PubChem BioAssay data set
NPT152	Individual protein	Nuclear factor erythroid 2-related factor 2	Homo sapiens	Potency	n.a.	53080.4	nM	PubChem BioAssay data set
NPT151	Individual protein	15-hydroxyprostaglandin dehydrogenase [NAD+]	Homo sapiens	Potency	=	14125.4	nM	PubChem BioAssay data set
NPT213	Individual protein	Cytochrome P450 2C19	Homo sapiens	AC50	=	398.11	nM	PubChem BioAssay data set
NPT11	Individual protein	Guanine nucleotide-binding protein G(s), subunit alpha	Homo sapiens	Potency	n.a.	1000.0	nM	PubChem BioAssay data set
NPT261	Individual protein	Monoamine oxidase A	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT212	Individual protein	Cytochrome P450 2C9	Homo sapiens	AC50	n.a.	n.a.	n.a.	PubChem BioAssay data set
NPT160	Individual protein	TAR DNA-binding protein 43	Homo sapiens	Potency	n.a.	3548.1	nM	PubChem BioAssay data set
NPT251	Individual protein	Histamine H1 receptor	Homo sapiens	AC50	=	17000.0	nM	PMID[37468498]
NPT2769	Individual protein	Thromboxane A2 receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT1197	Individual protein	Huntingtin	Homo sapiens	Potency	=	11220.2	nM	PubChem BioAssay data set
NPT295	Individual protein	Serotonin transporter	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT2769	Individual protein	Thromboxane A2 receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT108	Individual protein	Estrogen receptor alpha	Homo sapiens	Potency	n.a.	35481.3	nM	PubChem BioAssay data set
NPT103	Individual protein	Nuclear receptor ROR-gamma	Homo sapiens	Potency	n.a.	37578.0	nM	PubChem BioAssay data set
NPT222	Individual protein	Alpha-2a adrenergic receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT246	Individual protein	Dopamine transporter	Homo sapiens	AC50	=	16460.0	nM	PMID[37468498]
NPT145	Individual protein	Mu opioid receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT1788	Individual protein	Alpha-1a adrenergic receptor	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT1464	Individual protein	Phosphodiesterase 4D	Homo sapiens	AC50	=	25999.8	nM	PMID[37468498]
NPT290	Individual protein	Serotonin 2a (5-HT2a) receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT223	Individual protein	Alpha-2b adrenergic receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT272	Individual protein	Kappa opioid receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT264	Individual protein	Muscarinic acetylcholine receptor M3	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT271	Individual protein	Delta opioid receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT262	Individual protein	Muscarinic acetylcholine receptor M1	Homo sapiens	AC50	>	10000.0	nM	PMID[37468498]
NPT292	Individual protein	Serotonin 2c (5-HT2c) receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT135	Individual protein	Chromobox protein homolog 1	Homo sapiens	Potency	n.a.	89125.1	nM	PubChem BioAssay data set
NPT252	Individual protein	Histamine H2 receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT226	Individual protein	Beta-2 adrenergic receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT151	Individual protein	15-hydroxyprostaglandin dehydrogenase [NAD+]	Homo sapiens	Potency	=	8912.5	nM	PubChem BioAssay data set
NPT72	Individual protein	Solute carrier organic anion transporter family member 1B3	Homo sapiens	Inhibition	=	128.38	%	PMID[23571415]
NPT50	Individual protein	Tyrosyl-DNA phosphodiesterase 1	Homo sapiens	Potency	n.a.	33498.3	nM	PubChem BioAssay data set
NPT483	Individual protein	Prelamin-A/C	Homo sapiens	Potency	=	35481.3	nM	PubChem BioAssay data set
NPT987	Individual protein	Histamine H3 receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT50	Individual protein	Tyrosyl-DNA phosphodiesterase 1	Homo sapiens	Potency	n.a.	26608.6	nM	PubChem BioAssay data set
NPT94	Individual protein	Aldehyde dehydrogenase 1A1	Homo sapiens	Potency	=	31622.8	nM	PubChem BioAssay data set
NPT73	Individual protein	Solute carrier organic anion transporter family member 1B1	Homo sapiens	Inhibition	=	225.44	%	PMID[23571415]
NPT4064	Individual protein	Hormone-sensitive lipase	Rattus norvegicus	IC50	=	3250.0	nM	PMID[18808096]
NPT484	Individual protein	Luciferin 4-monooxygenase	Photinus pyralis	Potency	n.a.	16136.6	nM	PubChem BioAssay data set
NPT4064	Individual protein	Hormone-sensitive lipase	Rattus norvegicus	Inhibition	=	44.0	%	PMID[18808096]
NPT444	Individual protein	Ubiquitin carboxyl-terminal hydrolase 1	Homo sapiens	Potency	n.a.	63095.7	nM	PubChem BioAssay data set
NPT542	Individual protein	Progesterone receptor	Homo sapiens	AC50	=	25730.0	nM	PMID[37468498]
NPT98	Individual protein	HERG	Homo sapiens	Potency	n.a.	35481.3	nM	PubChem BioAssay data set
NPT20556	Single protein	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	21.89	%	Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen
NPT98	Individual protein	HERG	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT94	Individual protein	Aldehyde dehydrogenase 1A1	Homo sapiens	Potency	=	39810.7	nM	PubChem BioAssay data set
NPT484	Individual protein	Luciferin 4-monooxygenase	Photinus pyralis	Potency	n.a.	21331.3	nM	PubChem BioAssay data set
NPT29454	Single protein	Deoxynucleoside triphosphate triphosphohydrolase SAMHD1	Homo sapiens	Inhibition	=	0.9653	%	PMID[38318365]
NPT92	Individual protein	Serotonin 1a (5-HT1a) receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT5104	Individual protein	Phosphodiesterase 3A	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT63	Individual protein	Bromodomain adjacent to zinc finger domain protein 2B	Homo sapiens	Potency	n.a.	79432.8	nM	PubChem BioAssay data set
NPT670	Individual protein	Thrombin	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT546	Individual protein	Retinoid X receptor alpha	Homo sapiens	Potency	n.a.	14125.4	nM	PubChem BioAssay data set
NPT64	Individual protein	ATPase family AAA domain-containing protein 5	Homo sapiens	Potency	n.a.	18356.4	nM	PubChem BioAssay data set
NPT539	Individual protein	Cellular tumor antigen p53	Homo sapiens	Potency	n.a.	35481.3	nM	PubChem BioAssay data set
NPT546	Individual protein	Retinoid X receptor alpha	Homo sapiens	Potency	n.a.	44668.4	nM	PubChem BioAssay data set
NPT425	Individual protein	Serotonin 3a (5-HT3a) receptor	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT64	Individual protein	ATPase family AAA domain-containing protein 5	Homo sapiens	Potency	n.a.	16360.1	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT65	Cell line	HepG2	Homo sapiens	Activity	n.a.	n.a.	n.a.	PMID[31136174]
NPT65	Cell line	HepG2	Homo sapiens	%max	=	61.6	%	PMID[31136174]
NPT28438	Unchecked	Unchecked	n.a.	Potency	n.a.	35481.3	nM	PubChem BioAssay data set
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	IC50	>	19952.62	nM	Screening of ~5500 FDA-approved drugs and clinical candidates for anti-SARS-CoV-2 activity
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	0.0	%	Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Hit score	=	0.4514	n.a.	Identification of potential treatments for COVID-19 through artificial intelligence-enabled phenomic analysis of human cells infected with SARS-CoV-2
NPT28438	Unchecked	Unchecked	n.a.	Ac50	n.a.	39.81	uM	PubChem BioAssay data set
NPT28438	Unchecked	Unchecked	n.a.	SPF	=	1.0	n.a.	PMID[24690528]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	9285.0	nM	PubChem BioAssay data set
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	7375.3	nM	PubChem BioAssay data set
NPT28438	Unchecked	Unchecked	n.a.	AC50	n.a.	39810.7	nM	PubChem BioAssay data set
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	19011.5	nM	PubChem BioAssay data set
NPT28438	Unchecked	Unchecked	n.a.	Ratio	=	0.6	n.a.	PMID[24690528]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition index	=	0.3311	n.a.	In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	IC50	>	20000.0	nM	Screening of ~5500 FDA-approved drugs and clinical candidates for anti-SARS-CoV-2 activity
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	1.97	%	Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	15101.4	nM	PubChem BioAssay data set
NPT28438	Unchecked	Unchecked	n.a.	Potency	n.a.	16360.1	nM	PubChem BioAssay data set
NPT29392	Protein complex	Gamma-aminobutyric acid receptor subunit alpha-1/alpha-2/beta-2/gamma-2	Homo sapiens	AC50	>	30000.0	nM	PMID[37468498]
NPT634	Organism	Leishmania amazonensis	Leishmania amazonensis	IC50	=	4.9	ug.mL-1	PMID[23623672]
NPT29131	Unknown	Molecular identity unknown	n.a.	Potency	n.a.	50118.7	nM	PubChem BioAssay data set
NPT29131	Unknown	Molecular identity unknown	n.a.	Potency	n.a.	44668.4	nM	PubChem BioAssay data set
NPT20596	Phenotype	Hepatotoxicity	n.a.	Hepatotoxicity	n.a.	n.a.	n.a.	PMID[20014752]

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
-	Rattus norvegicus	NOAEL	=	429.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOAEL	=	393.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOAEL	=	600.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOAEL	>	789.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOAEL	>	10000.0	ppm	ToxVal
-	Rattus norvegicus	LD50	=	11600.0	mg/kg	ToxVal
-	Rattus norvegicus	LD50	>	12800.0	mg/kg	ToxVal
-	Rattus norvegicus	LEL	=	1525.0	mg/kg-day	ToxVal
-	Rattus norvegicus	LD50	=	7400.0	mg/kg	ToxVal
-	Rattus norvegicus	NOEL	<	196.0	mg/kg-day	ToxVal
-	Rattus norvegicus	NOEL	<	213.0	mg/kg-day	ToxVal
-	Mus musculus	NOAEL	=	5981.0	mg/kg-day	ToxVal
-	Mus musculus	NOAEL	=	7579.0	mg/kg-day	ToxVal
-	Mus musculus	NOAEL	=	4925.0	mg/kg-day	ToxVal
-	Mus musculus	LD50	>	1600.0	mg/kg	ToxVal
-	Oryctolagus cuniculus	LD50	>	16000.0	mg/kg	ToxVal
-	Homo sapiens	DNEL systemic	=	27.7	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 NPC599885 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	24797
0.1-0.2	19763
0.2-0.3	4842
0.3-0.4	425
0.4-0.5	25
0.5-0.6	3
0.6-0.7	1
0.7-0.8	1
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
0.675	Remote Similarity	NPC183655
0.5405	Remote Similarity	NPC78662
0.5263	Remote Similarity	NPC186098
0.5238	Remote Similarity	NPC131937

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC599885 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3620
0.1-0.2	5034
0.2-0.3	476
0.3-0.4	17
0.4-0.5	1
0.5-0.6	0
0.6-0.7	0
0.7-0.8	1
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	NPD1240	Phase 4
0.7778	Intermediate Similarity	NPD1607	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