NPASS Compound

Structure

NPC56058 OpenBabel07101718332D 62 65 0 0 1 0 0 0 0 0999 V2000 -2.5621 7.7205 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3546 -4.0015 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0882 1.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0882 -0.0570 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5490 -2.3972 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1544 6.0929 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0271 4.1687 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7468 4.4653 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8008 -1.3542 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6272 3.9571 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4897 -2.4555 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4372 -1.2205 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2845 4.2637 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6224 7.3785 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9586 -3.0833 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4487 6.3937 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0401 2.8575 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8379 1.7866 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5443 -0.9115 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5971 -0.0729 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5882 0.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5557 -2.2812 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2148 5.7509 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0852 3.1704 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.8072 4.1233 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.0348 -0.7114 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.8008 2.9723 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.1267 1.0836 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5443 3.0751 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5995 2.5296 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1596 -1.3629 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.0348 2.3295 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0411 4.7661 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.6353 -1.0883 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.5882 0.8090 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.6335 3.1385 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.5244 1.3545 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1267 0.5344 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3366 -0.2526 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6353 2.7064 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0852 -1.5524 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5995 -0.9115 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5443 -1.4570 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2465 -0.4908 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7617 1.5428 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.3366 1.8706 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.6335 -1.5205 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.0401 -1.2395 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.7405 2.6302 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1014 4.4241 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2324 -1.8905 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4974 1.5851 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2302 -0.7014 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2324 3.5085 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0271 -2.5507 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2575 4.0330 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5244 0.2635 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1596 2.9810 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3891 2.6802 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 -0.4106 0.4397 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 -1.0719 -0.6388 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 1 14 1 0 0 0 0 2 15 1 0 0 0 0 3 21 1 0 0 0 0 4 21 1 0 0 0 0 13 57 1 0 0 0 0 14 16 1 0 0 0 0 15 22 1 0 0 0 0 16 23 1 0 0 0 0 17 29 1 0 0 0 0 17 30 1 0 0 0 0 18 28 2 0 0 0 0 18 60 1 0 0 0 0 19 43 1 0 0 0 0 19 62 1 0 0 0 0 20 44 1 0 0 0 0 20 61 1 0 0 0 0 22 5 1 6 0 0 0 23 6 1 6 0 0 0 23 33 1 0 0 0 0 24 7 1 1 0 0 0 24 29 1 0 0 0 0 24 36 1 0 0 0 0 25 8 1 1 0 0 0 25 33 1 0 0 0 0 26 9 1 1 0 0 0 26 34 1 0 0 0 0 26 39 1 0 0 0 0 27 10 1 6 0 0 0 27 50 1 0 0 0 0 28 38 1 0 0 0 0 28 45 1 0 0 0 0 29 57 1 1 0 0 0 30 45 2 0 0 0 0 30 60 1 0 0 0 0 31 22 1 1 0 0 0 31 34 1 0 0 0 0 31 47 1 0 0 0 0 32 27 1 1 0 0 0 32 40 1 0 0 0 0 32 46 1 0 0 0 0 33 51 1 6 0 0 0 34 52 1 1 0 0 0 35 21 1 1 0 0 0 35 37 1 0 0 0 0 35 58 1 0 0 0 0 36 25 1 6 0 0 0 36 59 1 0 0 0 0 37 46 2 3 0 0 0 37 53 1 0 0 0 0 38 48 2 0 0 0 0 38 61 1 0 0 0 0 39 54 2 0 0 0 0 39 58 1 0 0 0 0 40 55 2 0 0 0 0 40 59 1 0 0 0 0 41 43 1 0 0 0 0 41 47 2 3 0 0 0 41 56 1 0 0 0 0 42 44 1 0 0 0 0 42 49 2 0 0 0 0 42 62 1 0 0 0 0 43 11 1 6 0 0 0 43 49 1 0 0 0 0 44 12 1 6 0 0 0 44 48 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	925.44
Volume:	912.675
LogP:	5.292
LogD:	5.101
LogS:	-4.421
# Rotatable Bonds:	10
TPSA:	218.33
# H-Bond Aceptor:	15
# H-Bond Donor:	5
# Rings:	4
# Heavy Atoms:	18

MedChem Properties

QED Drug-Likeness Score:	0.199
Synthetic Accessibility Score:	5.748
Fsp3:	0.795
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:	-5.234
MDCK Permeability:	1.6130623407661915e-05
Pgp-inhibitor:	1.0
Pgp-substrate:	0.993
Human Intestinal Absorption (HIA):	0.903
20% Bioavailability (F20%):	0.009
30% Bioavailability (F30%):	0.843

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.017
Plasma Protein Binding (PPB):	98.83550262451172%
Volume Distribution (VD):	0.992
Pgp-substrate:	4.324054718017578%

ADMET: Metabolism

CYP1A2-inhibitor:	0.023
CYP1A2-substrate:	0.429
CYP2C19-inhibitor:	0.133
CYP2C19-substrate:	0.84
CYP2C9-inhibitor:	0.153
CYP2C9-substrate:	0.009
CYP2D6-inhibitor:	0.003
CYP2D6-substrate:	0.031
CYP3A4-inhibitor:	0.946
CYP3A4-substrate:	0.921

ADMET: Excretion

Clearance (CL):	8.05
Half-life (T1/2):	0.088

ADMET: Toxicity

hERG Blockers:	0.032
Human Hepatotoxicity (H-HT):	0.903
Drug-inuced Liver Injury (DILI):	0.977
AMES Toxicity:	0.011
Rat Oral Acute Toxicity:	0.015
Maximum Recommended Daily Dose:	0.317
Skin Sensitization:	0.017
Carcinogencity:	0.044
Eye Corrosion:	0.003
Eye Irritation:	0.004
Respiratory Toxicity:	0.406

Download Data

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

Natural Product: NPC56058

Natural Product ID:	NPC56058
*Common Name:**	Hoiamide A
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	AJORQYDPWJZVAU-KCIYAEAGSA-N
Standard InCHI:	InChI=1S/C44H71N5O10S3/c1-14-16-23(6)33(51)25(8)36-24(7)29(57-13)17-30-45-28(18-60-30)38-48-44(12,20-61-38)42-49-43(11,19-62-42)41(56)47-31(22(5)15-2)34(52)26(9)39(54)58-35(21(3)4)37(53)46-32(27(10)50)40(55)59-36/h18,21-27,29,31-36,50-52H,14-17,19-20H2,1-13H3,(H,46,53)(H,47,56)/t22-,23+,24-,25-,26+,27+,29-,31-,32-,33-,34-,35-,36-,43+,44+/m0/s1
SMILES:	CCC[C@H]([C@@H]([C@@H]([C@H]1OC(=O)[C@@H](N=C(O)[C@@H](OC(=O)[C@H](C)[C@H](O)[C@@H](N=C([C@@]2(N=C([C@@]3(N=C(c4nc(C[C@@H]([C@@H]1C)OC)sc4)SC3)C)SC2)C)O)[C@H](CC)C)C(C)C)[C@H](O)C)C)O)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1215858
PubChem CID:	49864267
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0001813] Peptidomimetics [CHEMONTID:0001961] Depsipeptides [CHEMONTID:0001994] Cyclic depsipeptides

*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
NPO33200	symploca sp.	Species	Microcoleaceae	Bacteria	n.a.	n.a.	n.a.	PMID[12350160]
NPO33200	symploca sp.	Species	Microcoleaceae	Bacteria	n.a.	n.a.	n.a.	PMID[12762794]
NPO33200	symploca sp.	Species	Microcoleaceae	Bacteria	n.a.	Sunday Island, Papua New Guinea	n.a.	PMID[18163584]
NPO33200	symploca sp.	Species	Microcoleaceae	Bacteria	n.a.	Papua New Guinea	n.a.	PMID[20687534]
NPO33200	symploca sp.	Species	Microcoleaceae	Bacteria	n.a.	Panamanian	n.a.	PMID[24164245]
NPO33200	symploca sp.	Species	Microcoleaceae	Bacteria	n.a.	n.a.	n.a.	PMID[24588245]
NPO33200	symploca sp.	Species	Microcoleaceae	Bacteria	n.a.	n.a.	n.a.	PMID[28055219]
NPO33200	symploca sp.	Species	Microcoleaceae	Bacteria	n.a.	n.a.	n.a.	PMID[29808677]

☑ 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
EC50	1
IC50	3

Activity Type	# Activity
Cell Line	1
NON-MOLECULAR	1
Others	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT397	Cell Line	NCI-H460	Homo sapiens	IC50	=	11200.0	nM	PMID[529302]
NPT2	Others	Unspecified		EC50	=	1700.0	nM	PMID[529302]
NPT2	Others	Unspecified		IC50	=	45.6	nM	PMID[529302]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	2100.0	nM	PMID[529302]

☑ 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 NPC56058 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	197
0.1-0.2	2961
0.2-0.3	24312
0.3-0.4	13487
0.4-0.5	1569
0.5-0.6	104
0.6-0.7	55
0.7-0.8	10
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC522
0.7824	Intermediate Similarity	NPC473704
0.7765	Intermediate Similarity	NPC134480
0.7471	Intermediate Similarity	NPC475554
0.7429	Intermediate Similarity	NPC132662
0.7294	Intermediate Similarity	NPC210424
0.7241	Intermediate Similarity	NPC164006
0.7235	Intermediate Similarity	NPC216720
0.7222	Intermediate Similarity	NPC469801
0.7206	Intermediate Similarity	NPC469858
0.7124	Intermediate Similarity	NPC267605
0.6981	Remote Similarity	NPC74917
0.6943	Remote Similarity	NPC89592
0.6937	Remote Similarity	NPC120917
0.6928	Remote Similarity	NPC135558
0.6726	Remote Similarity	NPC475390
0.6688	Remote Similarity	NPC51692
0.6591	Remote Similarity	NPC127775
0.6591	Remote Similarity	NPC474538
0.657	Remote Similarity	NPC82436
0.657	Remote Similarity	NPC474068
0.657	Remote Similarity	NPC474103
0.657	Remote Similarity	NPC474064
0.6554	Remote Similarity	NPC231110
0.6552	Remote Similarity	NPC474515
0.6552	Remote Similarity	NPC206724
0.6532	Remote Similarity	NPC474079
0.6532	Remote Similarity	NPC474102
0.6532	Remote Similarity	NPC474080
0.6532	Remote Similarity	NPC475683
0.6532	Remote Similarity	NPC21449
0.6532	Remote Similarity	NPC157194
0.6517	Remote Similarity	NPC312887
0.6497	Remote Similarity	NPC52587
0.6494	Remote Similarity	NPC185665
0.6494	Remote Similarity	NPC474094
0.6494	Remote Similarity	NPC474067
0.6494	Remote Similarity	NPC475737
0.6477	Remote Similarity	NPC202591
0.6477	Remote Similarity	NPC212214
0.6457	Remote Similarity	NPC474090
0.6457	Remote Similarity	NPC109498
0.6457	Remote Similarity	NPC154873
0.6457	Remote Similarity	NPC163147
0.6457	Remote Similarity	NPC252616
0.6457	Remote Similarity	NPC61667
0.6457	Remote Similarity	NPC45576
0.6457	Remote Similarity	NPC32583
0.6441	Remote Similarity	NPC21126
0.6429	Remote Similarity	NPC101980
0.6429	Remote Similarity	NPC470146
0.6429	Remote Similarity	NPC97078
0.642	Remote Similarity	NPC268063
0.642	Remote Similarity	NPC224609
0.6395	Remote Similarity	NPC474069
0.6369	Remote Similarity	NPC214375
0.6369	Remote Similarity	NPC237219
0.6369	Remote Similarity	NPC103268
0.6301	Remote Similarity	NPC319751
0.6193	Remote Similarity	NPC119481
0.6173	Remote Similarity	NPC165538
0.6162	Remote Similarity	NPC24990
0.6136	Remote Similarity	NPC473398
0.6089	Remote Similarity	NPC50274
0.6073	Remote Similarity	NPC263485
0.6073	Remote Similarity	NPC25316
0.6073	Remote Similarity	NPC229160
0.6071	Remote Similarity	NPC122427
0.6071	Remote Similarity	NPC329961
0.6059	Remote Similarity	NPC474070
0.6057	Remote Similarity	NPC190329
0.6053	Remote Similarity	NPC161242
0.603	Remote Similarity	NPC239660
0.603	Remote Similarity	NPC106235
0.6021	Remote Similarity	NPC475330
0.599	Remote Similarity	NPC174652
0.5969	Remote Similarity	NPC475534
0.5969	Remote Similarity	NPC476080
0.587	Remote Similarity	NPC315252
0.582	Remote Similarity	NPC34319
0.581	Remote Similarity	NPC14877
0.581	Remote Similarity	NPC145178
0.581	Remote Similarity	NPC475350
0.574	Remote Similarity	NPC475604
0.5728	Remote Similarity	NPC251036
0.5707	Remote Similarity	NPC476103
0.5679	Remote Similarity	NPC201968
0.5673	Remote Similarity	NPC314254
0.5673	Remote Similarity	NPC313966
0.5661	Remote Similarity	NPC222391
0.5655	Remote Similarity	NPC475568
0.5654	Remote Similarity	NPC256912

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 NPC56058 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	113
0.1-0.2	728
0.2-0.3	4532
0.3-0.4	3261
0.4-0.5	492
0.5-0.6	17
0.6-0.7	7
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
0.7059	Intermediate Similarity	NPD6915	Approved
0.6774	Remote Similarity	NPD9579	Approved
0.6494	Remote Similarity	NPD6907	Phase 2
0.6441	Remote Similarity	NPD6910	Phase 3
0.6429	Remote Similarity	NPD6916	Clinical (unspecified phase)
0.6348	Remote Similarity	NPD6911	Discontinued
0.619	Remote Similarity	NPD2957	Phase 2
0.603	Remote Similarity	NPD8339	Clinical (unspecified phase)
0.5652	Remote Similarity	NPD7916	Approved
0.5652	Remote Similarity	NPD7915	Approved
0.5606	Remote Similarity	NPD7977	Clinical (unspecified phase)

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