NPASS Compound

Natural Product: NPC480317

Natural Product ID	NPC480317
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	XAVFGDZINHIWPZ-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	45271403
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 30 31 0 0 0 0 0 0 0 0999 V2000 -2.5458 1.1493 1.4749 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6287 1.0962 0.6375 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5194 0.2688 -0.4709 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3795 -0.4620 -0.7168 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3066 -0.3945 0.1335 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4032 0.4280 1.2439 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2946 -1.2307 -0.3381 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0159 -1.4219 0.2665 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0425 -0.3690 -0.0431 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3159 -0.2825 -1.5119 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3184 0.8089 -2.1178 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5780 -1.4296 -2.2577 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7820 0.9245 0.5113 N 0 0 0 0 0 0 0 0 0 0 0 0 2.5398 1.4910 1.5710 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5035 0.8420 2.0749 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2753 2.7570 2.1041 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7997 -1.7940 -1.4881 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0419 -1.3359 -1.7148 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.6081 1.7943 2.3554 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5126 1.6805 0.8544 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3749 0.2113 -1.1516 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5578 0.4904 1.9338 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4593 -2.4003 -0.0181 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9531 -1.4643 1.3963 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9892 -0.7376 0.4300 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1854 -1.4283 -3.0678 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9936 1.5328 0.1337 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0548 3.3395 2.4278 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3228 -2.5041 -2.1538 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7110 -1.5598 -2.4987 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 5 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 10 12 1 0 9 13 1 0 13 14 1 0 14 15 2 0 14 16 1 0 7 17 2 0 17 18 1 0 6 1 1 0 18 4 1 0 1 19 1 0 2 20 1 0 3 21 1 0 6 22 1 0 8 23 1 0 8 24 1 0 9 25 1 0 12 26 1 0 13 27 1 0 16 28 1 0 17 29 1 0 18 30 1 0 M END

Standard InCHIKey	XAVFGDZINHIWPZ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C12H12N2O4/c15-11(16)10(14-12(17)18)5-7-6-13-9-4-2-1-3-8(7)9/h1-4,6,10,13-14H,5H2,(H,15,16)(H,17,18)
SMILES	c1ccc2c(c1)c(CC(C(=O)O)NC(=O)O)c[nH]2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	248.08	Volume:	240.331 ? Van der Waals volume.
Dense:	1.032	LogP:	1.055 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.401 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.457 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	12.0
TPSA:	102.42 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	2.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.657	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.386	Fsp³:	0.167
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:	0.007	Fluc inhibitor:	0.282 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.158 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.286 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.021	Promiscuous compounds:	0.247

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.123	MDCK Permeability:	-4.606
Pgp-inhibitor:	0.0	Pgp-substrate:	0.002
PAMPA:	0.915 ? 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):	0.025
20% Bioavailability (F20%):	0.942	30% Bioavailability (F30%):	0.977
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.013	MRP1:	0.311
Plasma Protein Binding (PPB):	70.902%	Volume Distribution (VD):	-0.803
Fu:	24.208% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.967
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.001
BSEP inhibitor:	0.189

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.999	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.046	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.0
HLM stability:	0.01 ? 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):

1.151

Half-life (T1/2):

1.535

ADMET: Toxicity

hERG Blockers:	0.012	hERG Blockers (10um):	0.017
Human Hepatotoxicity (H-HT):	0.49	Drug-induced Liver Injury (DILI):	0.923
AMES Toxicity:	0.192	Rat Oral Acute Toxicity:	0.32
Maximum Recommended Daily Dose:	0.123	Skin Sensitization:	0.117
Carcinogencity:	0.148	Eye Corrosion:	0.002
Eye Irritation:	0.652	Respiratory Toxicity:	0.336
Drug-induced Neurotoxicity:	0.256	Ototoxicity:	0.721
Hematotoxicity:	0.266	Drug-induced Nephrotoxicity:	0.742
Genotoxicity:	0.914	RPMI-8226 Immunitoxicity:	0.015
A549 Cytotoxicity:	0.006	Hek293 Cytotoxicity:	0.01
BCF:	0.009 ? 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:	2.803 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.151 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.443 ? 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	<=	1.3	%	PMID[19113967]
NPT2960	Individual protein	Brevianamide F prenyltransferase	Aspergillus fumigatus	Activity	=	0.8	%	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	<=	0.8	%	PMID[19113967]
NPT2	Others	Unspecified	n.a.	Activity	=	26.0	%	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 NPC480317 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	39657
0.1-0.2	8915
0.2-0.3	940
0.3-0.4	228
0.4-0.5	90
0.5-0.6	14
0.6-0.7	10
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
0.66	Remote Similarity	NPC78020
0.6271	Remote Similarity	NPC605102
0.6154	Remote Similarity	NPC315555
0.6154	Remote Similarity	NPC55772
0.6102	Remote Similarity	NPC602969
0.6038	Remote Similarity	NPC149155
0.6038	Remote Similarity	NPC203468
0.6038	Remote Similarity	NPC110500
0.6038	Remote Similarity	NPC605329
0.6	Remote Similarity	NPC480316
0.5926	Remote Similarity	NPC480318
0.5818	Remote Similarity	NPC248041
0.5806	Remote Similarity	NPC606272
0.5614	Remote Similarity	NPC267885
0.5532	Remote Similarity	NPC601214
0.5424	Remote Similarity	NPC283219
0.54	Remote Similarity	NPC279081
0.5385	Remote Similarity	NPC111275
0.5283	Remote Similarity	NPC310665
0.52	Remote Similarity	NPC96102
0.5098	Remote Similarity	NPC230869
0.5088	Remote Similarity	NPC14113
0.5088	Remote Similarity	NPC145885
0.5088	Remote Similarity	NPC84827

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC480317 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5580
0.1-0.2	3376
0.2-0.3	141
0.3-0.4	42
0.4-0.5	8
0.5-0.6	2
0.6-0.7	1
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
0.6038	Remote Similarity	NPD482	Phase 4
0.5926	Remote Similarity	NPD749	Clinical (unspecified phase)
0.52	Remote Similarity	NPD198	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