NPASS Compound

Structure

NPC474064 OpenBabel07101719252D 33 34 0 0 1 0 0 0 0 0999 V2000 -1.8707 -3.9703 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0233 -1.1163 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2741 -2.1589 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1693 3.0362 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4563 1.5510 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1351 -0.0967 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9717 -2.5792 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0529 -2.9740 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6694 -1.8629 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1241 -2.6165 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4078 -1.9187 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6342 -0.4647 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0683 1.6451 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0191 -1.5861 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0529 -2.9871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0400 -0.9341 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9651 -1.2078 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9871 2.0529 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.6322 0.9846 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.2215 -0.5035 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6123 -0.6726 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9871 2.0399 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0131 -0.9999 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3706 0.9288 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0269 0.0658 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.9159 1.6824 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3555 -0.0035 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.7792 3.0180 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4681 1.4734 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0051 0.2737 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4605 2.5211 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 4.0136 -1.4816 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 1 15 1 0 0 0 0 3 17 1 0 0 0 0 6 20 1 0 0 0 0 7 8 1 0 0 0 0 7 9 1 0 0 0 0 8 15 1 0 0 0 0 9 16 1 0 0 0 0 10 11 1 0 0 0 0 10 15 2 0 0 0 0 11 23 1 0 0 0 0 12 17 2 0 0 0 0 12 21 1 0 0 0 0 13 22 1 0 0 0 0 13 24 1 0 0 0 0 14 21 2 0 0 0 0 14 33 1 0 0 0 0 16 2 1 6 0 0 0 16 25 1 0 0 0 0 18 4 1 6 0 0 0 18 22 1 0 0 0 0 18 26 1 0 0 0 0 19 5 1 1 0 0 0 19 25 1 0 0 0 0 19 26 1 0 0 0 0 20 27 2 0 0 0 0 20 33 1 0 0 0 0 21 27 1 0 0 0 0 22 28 1 1 0 0 0 23 17 1 6 0 0 0 23 32 1 0 0 0 0 24 29 2 0 0 0 0 24 32 1 0 0 0 0 25 30 1 6 0 0 0 26 31 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	477.25
Volume:	498.777
LogP:	3.219
LogD:	2.332
LogS:	-3.612
# Rotatable Bonds:	2
TPSA:	96.72
# H-Bond Aceptor:	6
# H-Bond Donor:	2
# Rings:	2
# Heavy Atoms:	7

MedChem Properties

QED Drug-Likeness Score:	0.466
Synthetic Accessibility Score:	4.981
Fsp3:	0.654
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.653
MDCK Permeability:	2.4064996978268027e-05
Pgp-inhibitor:	0.245
Pgp-substrate:	0.992
Human Intestinal Absorption (HIA):	0.021
20% Bioavailability (F20%):	0.295
30% Bioavailability (F30%):	0.771

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.395
Plasma Protein Binding (PPB):	93.05067443847656%
Volume Distribution (VD):	0.668
Pgp-substrate:	6.466133117675781%

ADMET: Metabolism

CYP1A2-inhibitor:	0.108
CYP1A2-substrate:	0.233
CYP2C19-inhibitor:	0.126
CYP2C19-substrate:	0.313
CYP2C9-inhibitor:	0.045
CYP2C9-substrate:	0.228
CYP2D6-inhibitor:	0.01
CYP2D6-substrate:	0.326
CYP3A4-inhibitor:	0.498
CYP3A4-substrate:	0.495

ADMET: Excretion

Clearance (CL):	11.775
Half-life (T1/2):	0.216

ADMET: Toxicity

hERG Blockers:	0.03
Human Hepatotoxicity (H-HT):	0.957
Drug-inuced Liver Injury (DILI):	0.937
AMES Toxicity:	0.015
Rat Oral Acute Toxicity:	0.75
Maximum Recommended Daily Dose:	0.292
Skin Sensitization:	0.245
Carcinogencity:	0.437
Eye Corrosion:	0.271
Eye Irritation:	0.018
Respiratory Toxicity:	0.951

Download Data

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

Natural Product: NPC474064

Natural Product ID:	NPC474064
*Common Name:**	Epothilone D1
IUPAC Name:	(4S,5R,7R,8S,9S,13Z,16S)-4,8-dihydroxy-5,7,9,13-tetramethyl-16-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-1-oxacyclohexadec-13-ene-2,6-dione
Synonyms:	Epothilone D1
Standard InCHIKey:	PPADMZQKLQKZMX-IJJUSYSYSA-N
Standard InCHI:	InChI=1S/C26H39NO5S/c1-15-8-7-9-16(2)25(30)19(5)26(31)18(4)22(28)13-24(29)32-23(11-10-15)17(3)12-21-14-33-20(6)27-21/h10,12,14,16,18-19,22-23,25,28,30H,7-9,11,13H2,1-6H3/b15-10-,17-12+/t16-,18+,19+,22-,23-,25-/m0/s1
SMILES:	CC1CCCC(=CCC(OC(=O)CC(C(C(=O)C(C1O)C)C)O)C(=CC2=CSC(=N2)C)C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL459626
PubChem CID:	9805055
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000147] Macrolides and analogues

*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
NPO32627	sorangium cellulosum, strains so ce90/b2	Species	Polyangiaceae	Bacteria	n.a.	n.a.	n.a.	PMID[11473410]

☑ 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
IC50	1

Activity Type	# Activity
Cell Line	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1460	Cell Line	L929	Mus musculus	IC50	=	0.035	ug.mL-1	PMID[538258]

☑ 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 NPC474064 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	166
0.1-0.2	806
0.2-0.3	4061
0.3-0.4	26292
0.4-0.5	11095
0.5-0.6	200
0.6-0.7	31
0.7-0.8	8
0.8-0.85	2
0.85-0.9	1
0.9-0.95	10
0.95-1	25

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC474103
1.0	High Similarity	NPC82436
1.0	High Similarity	NPC474068
0.9928	High Similarity	NPC157194
0.9928	High Similarity	NPC21449
0.9928	High Similarity	NPC474079
0.9928	High Similarity	NPC474080
0.9928	High Similarity	NPC474102
0.9928	High Similarity	NPC475683
0.9857	High Similarity	NPC475737
0.9857	High Similarity	NPC185665
0.9857	High Similarity	NPC474094
0.9787	High Similarity	NPC154873
0.9787	High Similarity	NPC252616
0.9787	High Similarity	NPC32583
0.9787	High Similarity	NPC109498
0.9787	High Similarity	NPC163147
0.9787	High Similarity	NPC45576
0.9787	High Similarity	NPC474090
0.9787	High Similarity	NPC61667
0.9718	High Similarity	NPC268063
0.9718	High Similarity	NPC224609
0.9716	High Similarity	NPC474067
0.9648	High Similarity	NPC206724
0.9648	High Similarity	NPC474515
0.964	High Similarity	NPC474069
0.9517	High Similarity	NPC127775
0.9514	High Similarity	NPC212214
0.9448	High Similarity	NPC21126
0.9384	High Similarity	NPC474538
0.9384	High Similarity	NPC52587
0.9379	High Similarity	NPC202591
0.932	High Similarity	NPC231110
0.9257	High Similarity	NPC312887
0.8592	High Similarity	NPC474070
0.8357	Intermediate Similarity	NPC475604
0.8143	Intermediate Similarity	NPC475568
0.7469	Intermediate Similarity	NPC315252
0.7436	Intermediate Similarity	NPC190329
0.7308	Intermediate Similarity	NPC469801
0.7278	Intermediate Similarity	NPC319751
0.7143	Intermediate Similarity	NPC119481
0.7108	Intermediate Similarity	NPC186452
0.7081	Intermediate Similarity	NPC473398
0.7066	Intermediate Similarity	NPC211555
0.6941	Remote Similarity	NPC12660
0.6901	Remote Similarity	NPC54983
0.686	Remote Similarity	NPC101980
0.686	Remote Similarity	NPC470146
0.686	Remote Similarity	NPC97078
0.657	Remote Similarity	NPC56058
0.657	Remote Similarity	NPC522
0.6474	Remote Similarity	NPC210424
0.6471	Remote Similarity	NPC165538
0.6452	Remote Similarity	NPC122427
0.6416	Remote Similarity	NPC216720
0.6364	Remote Similarity	NPC329961
0.6364	Remote Similarity	NPC469858
0.6348	Remote Similarity	NPC164006
0.6316	Remote Similarity	NPC14101
0.6271	Remote Similarity	NPC475554
0.6243	Remote Similarity	NPC473704
0.6231	Remote Similarity	NPC14877
0.6231	Remote Similarity	NPC145178
0.6231	Remote Similarity	NPC475350
0.6201	Remote Similarity	NPC24990
0.6188	Remote Similarity	NPC134480
0.6175	Remote Similarity	NPC132662
0.6139	Remote Similarity	NPC251036
0.6089	Remote Similarity	NPC473886
0.6087	Remote Similarity	NPC161242
0.6	Remote Similarity	NPC475390
0.6	Remote Similarity	NPC476080
0.6	Remote Similarity	NPC475534
0.5989	Remote Similarity	NPC476103
0.5979	Remote Similarity	NPC106235
0.5979	Remote Similarity	NPC239660
0.5953	Remote Similarity	NPC475196
0.5936	Remote Similarity	NPC263485
0.5936	Remote Similarity	NPC229160
0.5936	Remote Similarity	NPC25316
0.5882	Remote Similarity	NPC475330
0.5873	Remote Similarity	NPC161143
0.5851	Remote Similarity	NPC174652
0.5789	Remote Similarity	NPC478252
0.5789	Remote Similarity	NPC478251
0.5714	Remote Similarity	NPC267605
0.5676	Remote Similarity	NPC30527
0.5605	Remote Similarity	NPC201968

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 NPC474064 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	129
0.1-0.2	422
0.2-0.3	1664
0.3-0.4	5298
0.4-0.5	1547
0.5-0.6	81
0.6-0.7	4
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	2
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9857	High Similarity	NPD6907	Phase 2
0.9448	High Similarity	NPD6910	Phase 3
0.9184	High Similarity	NPD6911	Discontinued
0.8954	High Similarity	NPD6916	Clinical (unspecified phase)
0.8366	Intermediate Similarity	NPD6915	Approved
0.7047	Intermediate Similarity	NPD7496	Phase 2
0.65	Remote Similarity	NPD2957	Phase 2
0.6279	Remote Similarity	NPD5189	Clinical (unspecified phase)
0.6273	Remote Similarity	NPD1083	Clinical (unspecified phase)
0.6207	Remote Similarity	NPD5634	Approved
0.5979	Remote Similarity	NPD8339	Clinical (unspecified phase)
0.5956	Remote Similarity	NPD6870	Phase 1
0.5938	Remote Similarity	NPD6348	Clinical (unspecified phase)
0.5803	Remote Similarity	NPD6349	Phase 1
0.5745	Remote Similarity	NPD6641	Approved
0.5745	Remote Similarity	NPD6642	Approved
0.5707	Remote Similarity	NPD7977	Clinical (unspecified phase)
0.5663	Remote Similarity	NPD4949	Discontinued
0.5659	Remote Similarity	NPD8071	Approved
0.5615	Remote Similarity	NPD6739	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