NPASS Compound

Natural Product: NPC480324

Natural Product ID	NPC480324
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KZDNJQUJBMDHJW-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	44631736
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000211] Indoles and derivatives [CHEMONTID:0001290] Indolyl carboxylic acids and derivatives

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 28 0 0 0 0 0 0 0 0999 V2000 4.0718 0.3415 0.0535 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5162 -0.9029 0.1523 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1314 -1.0637 0.1033 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3207 0.0410 -0.0458 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9226 1.2827 -0.1421 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2886 1.4671 -0.0964 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0713 3.2151 -0.2351 Br 0 0 0 0 0 0 0 0 0 0 0 0 0.0136 -0.4082 -0.0622 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1283 0.5094 -0.2080 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4624 -0.1466 -0.2049 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5150 0.8815 -0.3576 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4559 0.9141 0.4678 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4848 1.8097 -1.3924 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7510 -0.9472 0.9278 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0447 -1.7745 0.0765 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3328 -2.1552 0.1753 N 0 0 0 0 0 0 0 0 0 0 0 0 5.1473 0.4417 0.0940 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1141 -1.8118 0.2717 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3058 2.1543 -0.2587 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9844 1.0759 -1.1428 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0864 1.2446 0.6245 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5268 -0.7870 -1.1341 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2417 2.4805 -1.4921 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3397 -0.4779 1.6481 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1347 -1.8847 0.6703 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8562 -2.3826 0.0952 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6863 -3.1166 0.2885 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 4 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 11 13 1 0 10 14 1 0 8 15 2 0 15 16 1 0 6 1 1 0 16 3 1 0 1 17 1 0 2 18 1 0 5 19 1 0 9 20 1 0 9 21 1 0 10 22 1 0 13 23 1 0 14 24 1 0 14 25 1 0 15 26 1 0 16 27 1 0 M END

Standard InCHIKey	KZDNJQUJBMDHJW-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C11H11BrN2O2/c12-7-1-2-10-8(4-7)6(5-14-10)3-9(13)11(15)16/h1-2,4-5,9,14H,3,13H2,(H,15,16)
SMILES	c1cc2c(cc1Br)c(CC(C(=O)O)N)c[nH]2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	282.0	Volume:	227.375 ? Van der Waals volume.
Dense:	1.24	LogP:	-0.147 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.684 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.919 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	11.0
TPSA:	79.11 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	4.0	Rings:	2.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.804	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.544	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:	0.263	Fluc inhibitor:	0.082 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.039 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.215 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.052	Promiscuous compounds:	0.634

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.359	MDCK Permeability:	-4.112
Pgp-inhibitor:	0.0	Pgp-substrate:	0.016
PAMPA:	0.831 ? 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%):	0.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.384	MRP1:	0.664
Plasma Protein Binding (PPB):	66.106%	Volume Distribution (VD):	-0.069
Fu:	26.693% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.97
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.0
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.822
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.424	CYP2C9-substrate:	0.015
CYP2D6-inhibitor:	0.991	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.019
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.82
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):

9.78

Half-life (T1/2):

1.208

ADMET: Toxicity

hERG Blockers:	0.115	hERG Blockers (10um):	0.279
Human Hepatotoxicity (H-HT):	0.431	Drug-induced Liver Injury (DILI):	0.161
AMES Toxicity:	0.337	Rat Oral Acute Toxicity:	0.677
Maximum Recommended Daily Dose:	0.735	Skin Sensitization:	0.158
Carcinogencity:	0.376	Eye Corrosion:	0.009
Eye Irritation:	0.582	Respiratory Toxicity:	0.549
Drug-induced Neurotoxicity:	0.695	Ototoxicity:	0.354
Hematotoxicity:	0.206	Drug-induced Nephrotoxicity:	0.336
Genotoxicity:	0.877	RPMI-8226 Immunitoxicity:	0.036
A549 Cytotoxicity:	0.044	Hek293 Cytotoxicity:	0.07
BCF:	0.487 ? 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:	3.191 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.509 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.812 ? 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
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17616609]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17929896]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19113967]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19159274]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19256529]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	isolated from sediment collected using a hand held deep water sampling device at >33 m depth in Vanuatu	2003	PMID[20303767]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21667925]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21954885]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22106303]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	stem bark of Melia azedarach	n.a.	n.a.	PMID[22409377]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23557488]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23563483]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7622436]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	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
Activity	4

Activity Type	# Activity
Individual protein	2
Others	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2960	Individual protein	Brevianamide F prenyltransferase	Aspergillus fumigatus	Activity	<=	1.9	%	PMID[19113967]
NPT2960	Individual protein	Brevianamide F prenyltransferase	Aspergillus fumigatus	Activity	<=	0.4	%	PMID[19113967]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified	n.a.	Activity	<=	1.2	%	PMID[19113967]
NPT2	Others	Unspecified	n.a.	Activity	<=	0.4	%	PMID[19113967]

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 NPC480324 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	36480
0.1-0.2	12279
0.2-0.3	878
0.3-0.4	184
0.4-0.5	19
0.5-0.6	7
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	NPC480325
0.7059	Intermediate Similarity	NPC480326
0.68	Remote Similarity	NPC149155
0.68	Remote Similarity	NPC203468
0.68	Remote Similarity	NPC110500
0.6667	Remote Similarity	NPC480321
0.6415	Remote Similarity	NPC45459
0.6415	Remote Similarity	NPC315491
0.6296	Remote Similarity	NPC262898
0.6296	Remote Similarity	NPC179701
0.5926	Remote Similarity	NPC480322
0.5636	Remote Similarity	NPC480320
0.5536	Remote Similarity	NPC602373
0.5472	Remote Similarity	NPC34844
0.5357	Remote Similarity	NPC248041
0.5357	Remote Similarity	NPC480323
0.52	Remote Similarity	NPC610648

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC480324 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3946
0.1-0.2	4782
0.2-0.3	376
0.3-0.4	38
0.4-0.5	6
0.5-0.6	0
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
0.68	Remote Similarity	NPD482	Phase 4
0.6415	Remote Similarity	NPD484	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