NPASS Compound

Natural Product: NPC113326

Natural Product ID	NPC113326
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(3S,6S,9S,12S)-3-Benzyl-9-Sec-Butyl-6-((2S,3R)-3-Hydroxybutan-2-Yl)-12-Isopropyl-1,4,7,10-Tetraazacyclododecane-2,5,8,11-Tetraone
IUPAC Name	(3S,6S,9S,12S)-3-benzyl-9-[(2S)-butan-2-yl]-6-[(2S,3R)-3-hydroxybutan-2-yl]-12-propan-2-yl-1,4,7,10-tetrazacyclododecane-2,5,8,11-tetrone
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL474037
PubChem CID	44572034
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000348] Peptides [CHEMONTID:0004831] Oligopeptides

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 75 76 0 0 0 0 0 0 0 0999 V2000 -4.7223 2.4240 -1.6521 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6748 2.1200 -0.6296 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5898 0.6469 -0.2745 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4786 0.5295 0.7702 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.2358 0.9742 0.2922 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.2871 1.5154 0.9453 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4359 1.7144 2.3078 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9771 1.9420 0.2698 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8049 1.8350 -1.1379 N 0 0 0 0 0 0 0 0 0 0 0 0 0.7898 0.8126 -1.8785 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6038 0.9546 -3.2303 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9677 -0.5429 -1.3110 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1179 -1.4060 -1.4999 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.8350 -2.1205 -0.7777 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6394 -2.2079 0.6964 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.8547 -1.7974 1.3098 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.5682 -0.8038 1.3671 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7505 -1.0156 2.2106 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3437 -3.6218 1.1420 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8655 -4.2509 0.5640 C 0 0 2 0 0 0 0 0 0 0 0 0 2.0555 -3.5876 0.8175 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7254 -4.7008 -0.8784 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1865 -3.5942 2.6515 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8491 -2.8587 -1.3787 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2856 -1.0894 -1.8859 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4134 -0.1976 -1.4927 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0958 -0.4237 -0.3078 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1428 0.3648 0.1176 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5415 1.4259 -0.6543 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8867 1.6702 -1.8241 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8236 0.8719 -2.2581 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3913 3.3431 0.6941 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2989 4.3441 0.3288 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6203 3.4264 2.1838 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9115 0.2024 0.3010 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4177 3.3684 -2.1888 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7787 1.6458 -2.4402 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7215 2.6560 -1.2176 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6850 2.4303 -1.0268 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9049 2.7017 0.2934 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3770 0.0656 -1.1675 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7807 1.2623 1.6040 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2872 2.0095 2.7365 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7747 1.2599 0.5997 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2278 1.7903 -3.6798 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1926 -0.4768 -0.2032 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1648 -1.5773 1.0533 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0940 -1.9371 2.3504 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2145 -4.3015 0.9409 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9909 -5.2503 1.1254 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6671 -4.0574 1.4424 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9999 -3.9222 -1.6071 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4538 -5.5415 -1.0973 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2621 -5.1576 -1.0623 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5269 -4.3833 3.0111 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1227 -3.7521 3.1926 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2899 -2.6200 2.9631 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2625 -2.4925 -2.2261 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4660 -2.0629 -1.4271 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2445 -1.1077 -2.9905 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8190 -1.2465 0.3301 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6410 0.1551 1.0361 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3758 2.0312 -0.2857 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1994 2.5018 -2.4306 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3344 1.0955 -3.1905 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3139 3.6070 0.1583 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2785 4.6530 1.2038 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3375 3.9268 -0.4971 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8000 5.2371 -0.1032 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8690 2.4046 2.5606 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7293 3.7542 2.7291 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4925 4.0861 2.3843 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0089 -0.9002 0.2676 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1021 0.6435 1.3030 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7459 0.6028 -0.3420 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 2 3 6 7 1 0 6 8 1 0 8 9 1 0 9 10 2 3 10 11 1 0 10 12 1 0 12 13 1 0 13 14 2 3 14 15 1 0 15 16 1 0 16 17 2 3 17 18 1 0 15 19 1 0 19 20 1 0 20 21 1 0 20 22 1 0 19 23 1 0 14 24 1 0 12 25 1 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 8 32 1 0 32 33 1 0 32 34 1 0 3 35 1 0 17 4 1 0 31 26 1 0 1 36 1 0 1 37 1 0 1 38 1 0 2 39 1 0 2 40 1 0 3 41 1 6 4 42 1 1 7 43 1 0 8 44 1 1 11 45 1 0 12 46 1 1 15 47 1 1 18 48 1 0 19 49 1 1 20 50 1 1 21 51 1 0 22 52 1 0 22 53 1 0 22 54 1 0 23 55 1 0 23 56 1 0 23 57 1 0 24 58 1 0 25 59 1 0 25 60 1 0 27 61 1 0 28 62 1 0 29 63 1 0 30 64 1 0 31 65 1 0 32 66 1 0 33 67 1 0 33 68 1 0 33 69 1 0 34 70 1 0 34 71 1 0 34 72 1 0 35 73 1 0 35 74 1 0 35 75 1 0 M END

Standard InCHIKey	ZWHILRBVKJAMNY-FELOTHHLSA-N
Standard InCHI	InChI=1S/C26H40N4O5/c1-7-15(4)21-25(34)30-22(16(5)17(6)31)26(35)27-19(13-18-11-9-8-10-12-18)23(32)28-20(14(2)3)24(33)29-21/h8-12,14-17,19-22,31H,7,13H2,1-6H3,(H,27,35)(H,28,32)(H,29,33)(H,30,34)/t15-,16+,17+,19-,20-,21-,22-/m0/s1
SMILES	CC[C@@H]([C@@H]1N=C(O)[C@@H](N=C(O)[C@@H](N=C([C@@H](N=C1O)[C@@H]([C@H](O)C)C)O)Cc1ccccc1)C(C)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	488.3	Volume:	510.622 ? Van der Waals volume.
Dense:	0.956	LogP:	1.497 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.019 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.146 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	18.0
TPSA:	150.59 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	5.0	Rings:	2.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.388	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.546	Fsp³:	0.615
MCE-18:	60.619 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.585	Fluc inhibitor:	0.152 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.078 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.701 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.017	Promiscuous compounds:	0.319

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.461	MDCK Permeability:	-4.987
Pgp-inhibitor:	0.949	Pgp-substrate:	0.998
PAMPA:	0.784 ? 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):	0.789
20% Bioavailability (F20%):	0.973	30% Bioavailability (F30%):	0.998
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.205
Plasma Protein Binding (PPB):	76.709%	Volume Distribution (VD):	-0.556
Fu:	21.655% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.984	BCRP inhibitor:	0.025
BSEP inhibitor:	0.974

ADMET: Metabolism

CYP1A2-inhibitor:	0.017	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.114	CYP2C19-substrate:	0.004
CYP2C9-inhibitor:	0.103	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.003	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.0
HLM stability:	0.216 ? 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):

3.046

Half-life (T1/2):

1.67

ADMET: Toxicity

hERG Blockers:	0.002	hERG Blockers (10um):	0.001
Human Hepatotoxicity (H-HT):	1.0	Drug-induced Liver Injury (DILI):	1.0
AMES Toxicity:	0.043	Rat Oral Acute Toxicity:	0.376
Maximum Recommended Daily Dose:	0.012	Skin Sensitization:	1.0
Carcinogencity:	0.168	Eye Corrosion:	0.0
Eye Irritation:	0.276	Respiratory Toxicity:	0.754
Drug-induced Neurotoxicity:	0.02	Ototoxicity:	0.992
Hematotoxicity:	0.452	Drug-induced Nephrotoxicity:	0.994
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.0
A549 Cytotoxicity:	0.0	Hek293 Cytotoxicity:	0.0
BCF:	0.339 ? 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:	3.13 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.675 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.647 ? 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
NPO33240	nonomuraea sp. ta-0426	Species	Streptosporangiaceae	Bacteria	n.a.	n.a.	n.a.	PMID[19013063]

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
IC50	3

Activity Type	# Activity
Cell line	1
Individual protein	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT6505	Individual protein	Galanin receptor 2	Rattus norvegicus	IC50	=	450.0	nM	PMID[25682561]
NPT6623	Individual protein	Galanin receptor 1	Rattus norvegicus	IC50	=	11.4	nM	PMID[7775984]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1125	Cell line	T98G	Homo sapiens	IC50	=	5.0	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

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 NPC113326 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	13568
0.1-0.2	33663
0.2-0.3	2320
0.3-0.4	224
0.4-0.5	60
0.5-0.6	13
0.6-0.7	4
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC224610
0.9545	High Similarity	NPC88267
0.8864	High Similarity	NPC194390
0.7955	Intermediate Similarity	NPC25565
0.7955	Intermediate Similarity	NPC475439
0.7273	Intermediate Similarity	NPC303045
0.6441	Remote Similarity	NPC483337
0.614	Remote Similarity	NPC254088
0.614	Remote Similarity	NPC486124
0.6034	Remote Similarity	NPC479753
0.5909	Remote Similarity	NPC311242
0.58	Remote Similarity	NPC161972
0.5797	Remote Similarity	NPC287401
0.5625	Remote Similarity	NPC621
0.5571	Remote Similarity	NPC252878
0.5439	Remote Similarity	NPC100825
0.5345	Remote Similarity	NPC479749
0.5294	Remote Similarity	NPC82963
0.5238	Remote Similarity	NPC487595
0.5205	Remote Similarity	NPC489824
0.5161	Remote Similarity	NPC487313
0.5143	Remote Similarity	NPC489593
0.5077	Remote Similarity	NPC237420

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC113326 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	1876
0.1-0.2	6551
0.2-0.3	667
0.3-0.4	51
0.4-0.5	5
0.5-0.6	0
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
		NPD

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