NPASS Compound

Structure

NPC235078 OpenBabel07101718242D 43 42 0 0 1 0 0 0 0 0999 V2000 6.0622 -3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -4.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -4.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -4.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -3.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7321 2.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7321 -1.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8660 1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8660 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -3.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 1.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -2.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 2.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 14 3 0 0 0 0 2 19 1 0 0 0 0 3 19 1 0 0 0 0 4 20 1 0 0 0 0 5 20 1 0 0 0 0 6 21 1 0 0 0 0 7 21 1 0 0 0 0 8 22 1 0 0 0 0 9 22 1 0 0 0 0 10 34 1 0 0 0 0 11 35 1 0 0 0 0 12 36 1 0 0 0 0 13 37 1 0 0 0 0 14 15 1 0 0 0 0 15 16 1 0 0 0 0 16 17 1 0 0 0 0 17 23 1 0 0 0 0 18 23 1 0 0 0 0 18 24 1 0 0 0 0 23 38 2 0 0 0 0 24 34 1 0 0 0 0 24 39 2 0 0 0 0 25 19 1 6 0 0 0 25 29 1 0 0 0 0 25 35 1 0 0 0 0 26 20 1 6 0 0 0 26 30 1 0 0 0 0 26 34 1 0 0 0 0 27 21 1 6 0 0 0 27 31 1 0 0 0 0 27 37 1 0 0 0 0 28 22 1 6 0 0 0 28 32 1 0 0 0 0 28 36 1 0 0 0 0 29 33 2 0 0 0 0 29 40 1 0 0 0 0 30 36 1 0 0 0 0 30 41 2 0 0 0 0 31 35 1 0 0 0 0 31 42 2 0 0 0 0 32 37 1 0 0 0 0 32 43 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	605.42
Volume:	648.661
LogP:	2.224
LogD:	0.676
LogS:	-2.712
# Rotatable Bonds:	21
TPSA:	141.4
# H-Bond Aceptor:	11
# H-Bond Donor:	2
# Rings:	0
# Heavy Atoms:	11

MedChem Properties

QED Drug-Likeness Score:	0.153
Synthetic Accessibility Score:	4.559
Fsp3:	0.75
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.242
MDCK Permeability:	1.1868794899783097e-05
Pgp-inhibitor:	0.99
Pgp-substrate:	0.133
Human Intestinal Absorption (HIA):	0.97
20% Bioavailability (F20%):	0.049
30% Bioavailability (F30%):	0.912

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.95
Plasma Protein Binding (PPB):	89.36722564697266%
Volume Distribution (VD):	0.82
Pgp-substrate:	12.267768859863281%

ADMET: Metabolism

CYP1A2-inhibitor:	0.0
CYP1A2-substrate:	0.069
CYP2C19-inhibitor:	0.035
CYP2C19-substrate:	0.855
CYP2C9-inhibitor:	0.079
CYP2C9-substrate:	0.071
CYP2D6-inhibitor:	0.028
CYP2D6-substrate:	0.071
CYP3A4-inhibitor:	0.825
CYP3A4-substrate:	0.919

ADMET: Excretion

Clearance (CL):	5.1
Half-life (T1/2):	0.502

ADMET: Toxicity

hERG Blockers:	0.004
Human Hepatotoxicity (H-HT):	0.871
Drug-inuced Liver Injury (DILI):	0.974
AMES Toxicity:	0.01
Rat Oral Acute Toxicity:	0.007
Maximum Recommended Daily Dose:	0.036
Skin Sensitization:	0.179
Carcinogencity:	0.002
Eye Corrosion:	0.003
Eye Irritation:	0.006
Respiratory Toxicity:	0.157

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC235078

Natural Product ID:	NPC235078
*Common Name:**	Dragonamide D
IUPAC Name:	N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]-N-methyl-3-oxooct-7-ynamide
Synonyms:	Dragonamide D
Standard InCHIKey:	AGFCKPZYFBZCBZ-LJWNLINESA-N
Standard InCHI:	InChI=1S/C32H55N5O6/c1-14-15-16-17-23(38)18-24(39)34(10)26(20(4)5)30(41)36(12)28(22(8)9)32(43)37(13)27(21(6)7)31(42)35(11)25(19(2)3)29(33)40/h1,19-22,25-28H,15-18H2,2-13H3,(H2,33,40)/t25-,26-,27-,28-/m0/s1
SMILES:	C#CCCCC(=O)CC(=O)N([C@H](C(=O)N([C@H](C(=O)N([C@H](C(=O)N([C@H](C(=N)O)C(C)C)C)C(C)C)C)C(C)C)C)C(C)C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL510715
PubChem CID:	24878793
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:0000347] Amino acids and derivatives [CHEMONTID:0000060] Alpha amino acids and derivatives [CHEMONTID:0004310] Valine and derivatives

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO17326	Lyngbya polychroa	Species	Oscillatoriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[18393465]
NPO17326	Lyngbya polychroa	Species	Oscillatoriaceae	Bacteria	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	NP ID	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
GI50	3

Activity Type	# Activity
Cell Line	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1045	Cell Line	U2OS	Homo sapiens	GI50	=	59000.0	nM	PMID[507380]
NPT139	Cell Line	HT-29	Homo sapiens	GI50	=	32000.0	nM	PMID[507380]
NPT744	Cell Line	IMR-32	Homo sapiens	GI50	=	51000.0	nM	PMID[507380]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC235078 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	228
0.1-0.2	20743
0.2-0.3	18011
0.3-0.4	2630
0.4-0.5	763
0.5-0.6	249
0.6-0.7	68
0.7-0.8	2
0.8-0.85	0
0.85-0.9	1
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9231	High Similarity	NPC23984
0.8889	High Similarity	NPC472351
0.7356	Intermediate Similarity	NPC53858
0.7356	Intermediate Similarity	NPC84128
0.7053	Intermediate Similarity	NPC38172
0.703	Intermediate Similarity	NPC323720
0.6832	Remote Similarity	NPC124554
0.6832	Remote Similarity	NPC301148
0.6832	Remote Similarity	NPC5864
0.6699	Remote Similarity	NPC128303
0.6667	Remote Similarity	NPC47076
0.6667	Remote Similarity	NPC134504
0.6635	Remote Similarity	NPC241394
0.6629	Remote Similarity	NPC31756
0.6602	Remote Similarity	NPC198344
0.6593	Remote Similarity	NPC6902
0.6593	Remote Similarity	NPC284456
0.6556	Remote Similarity	NPC476156
0.6556	Remote Similarity	NPC476137
0.6556	Remote Similarity	NPC476117
0.6556	Remote Similarity	NPC476243
0.6538	Remote Similarity	NPC124549
0.6526	Remote Similarity	NPC473495
0.6509	Remote Similarity	NPC67009
0.6495	Remote Similarity	NPC474576
0.6484	Remote Similarity	NPC476302
0.6437	Remote Similarity	NPC256312
0.6437	Remote Similarity	NPC161774
0.6437	Remote Similarity	NPC266888
0.6437	Remote Similarity	NPC209156
0.6429	Remote Similarity	NPC173763
0.6429	Remote Similarity	NPC62263
0.6429	Remote Similarity	NPC471098
0.6413	Remote Similarity	NPC184473
0.6395	Remote Similarity	NPC196007
0.6395	Remote Similarity	NPC76297
0.6395	Remote Similarity	NPC214532
0.6392	Remote Similarity	NPC475801
0.6392	Remote Similarity	NPC474593
0.6373	Remote Similarity	NPC220234
0.6364	Remote Similarity	NPC301010
0.63	Remote Similarity	NPC280066
0.6235	Remote Similarity	NPC250953
0.618	Remote Similarity	NPC327272
0.6176	Remote Similarity	NPC473597
0.6146	Remote Similarity	NPC477539
0.6129	Remote Similarity	NPC470783
0.6122	Remote Similarity	NPC275715
0.6122	Remote Similarity	NPC155230
0.61	Remote Similarity	NPC315237
0.6087	Remote Similarity	NPC312315
0.6078	Remote Similarity	NPC117829
0.6064	Remote Similarity	NPC246005
0.6058	Remote Similarity	NPC475440
0.6055	Remote Similarity	NPC207820
0.6	Remote Similarity	NPC222466
0.5983	Remote Similarity	NPC160688
0.5978	Remote Similarity	NPC473741
0.5978	Remote Similarity	NPC477145
0.595	Remote Similarity	NPC101719
0.5948	Remote Similarity	NPC477237
0.5922	Remote Similarity	NPC469739
0.5909	Remote Similarity	NPC171734
0.5888	Remote Similarity	NPC475149
0.5888	Remote Similarity	NPC471097
0.5882	Remote Similarity	NPC262615
0.5862	Remote Similarity	NPC306696
0.5849	Remote Similarity	NPC13175
0.5849	Remote Similarity	NPC475791
0.5847	Remote Similarity	NPC477238
0.5842	Remote Similarity	NPC477538
0.5833	Remote Similarity	NPC470653
0.5833	Remote Similarity	NPC470654
0.5833	Remote Similarity	NPC470650
0.5833	Remote Similarity	NPC476877
0.5814	Remote Similarity	NPC128005
0.5814	Remote Similarity	NPC84182
0.58	Remote Similarity	NPC322966
0.5795	Remote Similarity	NPC322274
0.5755	Remote Similarity	NPC475758
0.5727	Remote Similarity	NPC475637
0.5727	Remote Similarity	NPC476876
0.5714	Remote Similarity	NPC178919
0.5714	Remote Similarity	NPC263281
0.57	Remote Similarity	NPC324506
0.5699	Remote Similarity	NPC59867
0.569	Remote Similarity	NPC296043
0.5686	Remote Similarity	NPC476019
0.5663	Remote Similarity	NPC34838
0.5663	Remote Similarity	NPC292299
0.5657	Remote Similarity	NPC319913
0.5647	Remote Similarity	NPC105297
0.5641	Remote Similarity	NPC329216
0.5638	Remote Similarity	NPC191774
0.5632	Remote Similarity	NPC287693
0.5625	Remote Similarity	NPC475542
0.5618	Remote Similarity	NPC212866
0.5618	Remote Similarity	NPC29598
0.561	Remote Similarity	NPC22746
0.5607	Remote Similarity	NPC475188
0.5603	Remote Similarity	NPC472536
0.5603	Remote Similarity	NPC103391
0.56	Remote Similarity	NPC322672

Chemically structural similarity: II. Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC235078 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	83
0.1-0.2	2622
0.2-0.3	4936
0.3-0.4	1154
0.4-0.5	292
0.5-0.6	47
0.6-0.7	16
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
0.7045	Intermediate Similarity	NPD7762	Phase 2
0.7045	Intermediate Similarity	NPD7763	Phase 2
0.6966	Remote Similarity	NPD2683	Discontinued
0.6951	Remote Similarity	NPD620	Approved
0.6848	Remote Similarity	NPD7760	Phase 2
0.6848	Remote Similarity	NPD7759	Phase 2
0.6735	Remote Similarity	NPD7841	Clinical (unspecified phase)
0.6598	Remote Similarity	NPD6699	Clinical (unspecified phase)
0.6571	Remote Similarity	NPD6937	Approved
0.6535	Remote Similarity	NPD4825	Clinical (unspecified phase)
0.6495	Remote Similarity	NPD4780	Clinical (unspecified phase)
0.6495	Remote Similarity	NPD4261	Phase 1
0.6421	Remote Similarity	NPD3176	Clinical (unspecified phase)
0.6316	Remote Similarity	NPD3723	Clinical (unspecified phase)
0.6186	Remote Similarity	NPD3177	Phase 3
0.6162	Remote Similarity	NPD2682	Approved
0.6154	Remote Similarity	NPD6120	Clinical (unspecified phase)
0.6117	Remote Similarity	NPD8038	Phase 2
0.6064	Remote Similarity	NPD1125	Discovery
0.6	Remote Similarity	NPD9425	Approved
0.6	Remote Similarity	NPD5792	Clinical (unspecified phase)
0.5981	Remote Similarity	NPD6122	Discontinued
0.5962	Remote Similarity	NPD3714	Approved
0.5962	Remote Similarity	NPD3715	Approved
0.5962	Remote Similarity	NPD3713	Approved
0.5917	Remote Similarity	NPD8041	Phase 2
0.5882	Remote Similarity	NPD6438	Approved
0.5882	Remote Similarity	NPD6437	Approved
0.5875	Remote Similarity	NPD4281	Clinical (unspecified phase)
0.5849	Remote Similarity	NPD5359	Clinical (unspecified phase)
0.5816	Remote Similarity	NPD5791	Phase 2
0.5789	Remote Similarity	NPD612	Discontinued
0.5778	Remote Similarity	NPD6944	Clinical (unspecified phase)
0.5773	Remote Similarity	NPD3733	Clinical (unspecified phase)
0.5745	Remote Similarity	NPD4815	Discontinued
0.573	Remote Similarity	NPD2220	Clinical (unspecified phase)
0.5714	Remote Similarity	NPD1784	Approved
0.5682	Remote Similarity	NPD322	Phase 1
0.5679	Remote Similarity	NPD1456	Approved
0.5638	Remote Similarity	NPD4278	Clinical (unspecified phase)
0.5618	Remote Similarity	NPD7840	Approved
0.5604	Remote Similarity	NPD265	Phase 3
0.5604	Remote Similarity	NPD266	Phase 3

Bioactivity similarity: Similar Natural Products in NPASS

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