NPASS Compound

Natural Product: NPC604998

Natural Product ID	NPC604998
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	BNZYRKVSCLSXSJ-IOSLPCCCSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL453867
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 36 38 0 0 0 0 0 0 0 0999 V2000 5.3050 0.9346 0.0676 N 0 0 0 0 0 0 0 0 0 0 0 0 4.0128 0.8492 0.6238 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7130 1.1686 1.8972 N 0 0 0 0 0 0 0 0 0 0 0 0 2.4425 1.0625 2.3691 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4269 0.6346 1.5891 N 0 0 0 0 0 0 0 0 0 0 0 0 1.6783 0.3020 0.3026 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9688 0.4113 -0.1717 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9080 0.0193 -1.4546 N 0 0 0 0 0 0 0 0 0 0 0 0 1.6509 -0.3195 -1.7763 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8619 -0.1515 -0.6940 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.5488 -0.4011 -0.6151 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9628 -1.1984 -1.8349 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2911 -1.5391 -1.8419 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3021 0.7658 -0.6021 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5037 0.4994 -0.0062 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.8693 1.7008 0.8682 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9468 2.7931 0.0061 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3583 -0.7080 0.8656 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3299 -1.6358 0.5806 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9585 -1.1917 0.5964 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9298 -2.5587 0.3034 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8794 0.0820 -0.0112 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6834 1.8344 -0.2607 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3119 1.3450 3.4076 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3644 -0.6693 -2.7694 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3008 -2.0800 -1.9502 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7606 -0.5576 -2.7312 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7931 -1.0542 -2.5676 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3414 0.3746 -0.7181 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8489 1.5170 1.3629 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0452 1.8353 1.6009 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2839 2.7278 -0.7318 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4841 -0.4291 1.9520 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0483 -2.5651 0.5946 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3205 -0.9761 1.4770 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0203 -2.8222 0.2725 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 1 0 11 12 1 6 12 13 1 0 11 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 15 18 1 0 18 19 1 0 18 20 1 0 20 21 1 0 7 2 1 0 20 11 1 0 10 6 1 0 1 22 1 0 1 23 1 0 4 24 1 0 9 25 1 0 12 26 1 0 12 27 1 0 13 28 1 0 15 29 1 6 16 30 1 0 16 31 1 0 17 32 1 0 18 33 1 1 19 34 1 0 20 35 1 1 21 36 1 0 M END

Standard InCHIKey	BNZYRKVSCLSXSJ-IOSLPCCCSA-N
Standard InCHI	InChI=1S/C11H15N5O5/c12-9-6-10(14-3-13-9)16(4-15-6)11(2-18)8(20)7(19)5(1-17)21-11/h3-5,7-8,17-20H,1-2H2,(H2,12,13,14)/t5-,7-,8-,11-/m1/s1
SMILES	Nc1ncnc2c1ncn2[C@]1(CO)O[C@H](CO)[C@@H](O)[C@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	297.11	Volume:	261.532 ? Van der Waals volume.
Dense:	1.136	LogP:	-0.862 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.356 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.56 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	15.0
TPSA:	159.77 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	6.0	Rings:	3.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.402	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.195	Fsp³:	0.545
MCE-18:	65.941 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.05	Fluc inhibitor:	0.018 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.048 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.021 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.047	Promiscuous compounds:	0.052

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.071	MDCK Permeability:	-5.27
Pgp-inhibitor:	0.0	Pgp-substrate:	0.754
PAMPA:	0.978 ? 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):	0.119
20% Bioavailability (F20%):	0.054	30% Bioavailability (F30%):	0.551
50% Bioavailability (F50%):	0.696

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.364	MRP1:	0.143
Plasma Protein Binding (PPB):	28.996%	Volume Distribution (VD):	-0.29
Fu:	72.001% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.985
OATP1B3 inhibitor:	0.99	BCRP inhibitor:	0.02
BSEP inhibitor:	0.001

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.01	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.008	CYP2D6-substrate:	0.012
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.019
HLM stability:	0.004 ? 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):

4.827

Half-life (T1/2):

2.734

ADMET: Toxicity

hERG Blockers:	0.043	hERG Blockers (10um):	0.144
Human Hepatotoxicity (H-HT):	0.768	Drug-induced Liver Injury (DILI):	0.911
AMES Toxicity:	0.926	Rat Oral Acute Toxicity:	0.113
Maximum Recommended Daily Dose:	0.181	Skin Sensitization:	0.992
Carcinogencity:	0.876	Eye Corrosion:	0.0
Eye Irritation:	0.635	Respiratory Toxicity:	0.507
Drug-induced Neurotoxicity:	0.695	Ototoxicity:	0.837
Hematotoxicity:	0.643	Drug-induced Nephrotoxicity:	0.639
Genotoxicity:	0.977	RPMI-8226 Immunitoxicity:	0.147
A549 Cytotoxicity:	0.115	Hek293 Cytotoxicity:	0.397
BCF:	-0.072 ? 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:	1.776 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.553 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	2.374 ? 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
NPO60972	Streptomyces hygroscopicus var. angustmyceticus	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
Inhibition	1
Activity	1
IC50	2

Activity Type	# Activity
Individual protein	2
Organism	1
Single protein	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2784	Individual protein	GMP synthase [glutamine-hydrolyzing]	Homo sapiens	IC50	=	17300.0	nM	PMID[30964283]
NPT892	Individual protein	Monoamine oxidase A	Mus musculus	Activity	n.a.	n.a.	n.a.	PMID[18834112]
NPT24672	Single protein	Glutamine amidotransferase	Plasmodium falciparum	Inhibition	=	25.0	%	PMID[30964283]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	300000.0	nM	PMID[30964283]

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	LD50	=	10000.0	mg/kg	ToxVal
-	Mus musculus	LD50	=	13.0	mg/kg	ToxVal
-	Cavia porcellus	LD50	>	10000.0	mg/kg	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 NPC604998 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	37621
0.1-0.2	12057
0.2-0.3	84
0.3-0.4	47
0.4-0.5	34
0.5-0.6	10
0.6-0.7	4
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
0.7222	Intermediate Similarity	NPC607315
0.6034	Remote Similarity	NPC156461
0.6034	Remote Similarity	NPC107374
0.6034	Remote Similarity	NPC600382
0.6034	Remote Similarity	NPC612067
0.569	Remote Similarity	NPC317821
0.5667	Remote Similarity	NPC209525
0.5667	Remote Similarity	NPC161659
0.5574	Remote Similarity	NPC609472
0.5484	Remote Similarity	NPC309832
0.541	Remote Similarity	NPC229974
0.5246	Remote Similarity	NPC33996
0.5077	Remote Similarity	NPC136349
0.5077	Remote Similarity	NPC219313
0.5075	Remote Similarity	NPC211025

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC604998 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7247
0.1-0.2	1752
0.2-0.3	94
0.3-0.4	37
0.4-0.5	16
0.5-0.6	1
0.6-0.7	2
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
0.6034	Remote Similarity	NPD249	Phase 4
0.6034	Remote Similarity	NPD250	Phase 4
0.5077	Remote Similarity	NPD548	Clinical (unspecified phase)

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