NPASS Compound

Structure

NPC248454 OpenBabel07101718282D 23 25 0 0 1 0 0 0 0 0999 V2000 1.3660 -2.3660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3660 -2.3660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1884 0.8741 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0700 -0.9945 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5240 -0.1035 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0714 -1.0468 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9794 0.7352 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8320 -0.7588 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3826 0.9360 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5391 -0.0517 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5267 -0.2081 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9807 0.6829 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 -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 2 0 0 0 0 0 0 0 0 0 -0.8660 -0.5000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.2736 1.3900 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 0.0000 -0.0000 0.0000 N 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 -1.7321 -2.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8660 -1.5000 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 -0.7355 0.4914 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 2 22 1 0 0 0 0 3 23 1 0 0 0 0 4 5 2 0 0 0 0 4 6 1 0 0 0 0 5 7 1 0 0 0 0 6 11 2 0 0 0 0 7 12 2 0 0 0 0 8 10 1 0 0 0 0 9 10 2 0 0 0 0 9 17 1 0 0 0 0 10 11 1 0 0 0 0 11 12 1 0 0 0 0 12 17 1 0 0 0 0 13 15 1 0 0 0 0 13 19 2 0 0 0 0 13 20 1 0 0 0 0 14 16 1 0 0 0 0 14 18 2 0 0 0 0 14 21 1 0 0 0 0 15 1 1 1 0 0 0 15 18 1 0 0 0 0 15 22 1 0 0 0 0 16 8 1 1 0 0 0 16 19 1 0 0 0 0 16 23 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	349.09
Volume:	331.393
LogP:	2.408
LogD:	2.455
LogS:	-3.346
# Rotatable Bonds:	4
TPSA:	73.99
# H-Bond Aceptor:	5
# H-Bond Donor:	3
# Rings:	3
# Heavy Atoms:	7

MedChem Properties

QED Drug-Likeness Score:	0.79
Synthetic Accessibility Score:	4.192
Fsp3:	0.375
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.065
MDCK Permeability:	1.47736545841326e-05
Pgp-inhibitor:	0.0
Pgp-substrate:	0.346
Human Intestinal Absorption (HIA):	0.009
20% Bioavailability (F20%):	0.001
30% Bioavailability (F30%):	0.001

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.855
Plasma Protein Binding (PPB):	93.89796447753906%
Volume Distribution (VD):	1.186
Pgp-substrate:	8.746244430541992%

ADMET: Metabolism

CYP1A2-inhibitor:	0.359
CYP1A2-substrate:	0.93
CYP2C19-inhibitor:	0.932
CYP2C19-substrate:	0.791
CYP2C9-inhibitor:	0.801
CYP2C9-substrate:	0.865
CYP2D6-inhibitor:	0.487
CYP2D6-substrate:	0.114
CYP3A4-inhibitor:	0.59
CYP3A4-substrate:	0.925

ADMET: Excretion

Clearance (CL):	11.053
Half-life (T1/2):	0.537

ADMET: Toxicity

hERG Blockers:	0.003
Human Hepatotoxicity (H-HT):	0.198
Drug-inuced Liver Injury (DILI):	0.948
AMES Toxicity:	0.007
Rat Oral Acute Toxicity:	0.477
Maximum Recommended Daily Dose:	0.26
Skin Sensitization:	0.267
Carcinogencity:	0.131
Eye Corrosion:	0.003
Eye Irritation:	0.01
Respiratory Toxicity:	0.024

Download Data

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

Natural Product: NPC248454

Natural Product ID:	NPC248454
*Common Name:**	3,6 Bismethyl(Thiocyclo)Alanyltryptophyl
IUPAC Name:	(3S,6S)-3-(1H-indol-3-ylmethyl)-6-methyl-3,6-bis(methylsulfanyl)piperazine-2,5-dione
Synonyms:	3,6 Bismethyl(Thiocyclo)Alanyltryptophyl
Standard InCHIKey:	WZCXTZDWTILORX-HOTGVXAUSA-N
Standard InCHI:	InChI=1S/C16H19N3O2S2/c1-15(22-2)13(20)19-16(23-3,14(21)18-15)8-10-9-17-12-7-5-4-6-11(10)12/h4-7,9,17H,8H2,1-3H3,(H,18,21)(H,19,20)/t15-,16-/m0/s1
SMILES:	CS[C@@]1(N=C(O)[C@](N=C1O)(C)SC)Cc1c[nH]c2c1cccc2
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1089314
PubChem CID:	21575389
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

*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
NPO333	Nectria inventa	Species	Nectriaceae	Eukaryota	n.a.	isolated from sediment collected by dredge at >600 m in the Monterey Bay trench	n.a.	PMID[20303767]
NPO333	Nectria inventa	Species	Nectriaceae	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	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
Organism	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT471	Organism	Trypanosoma brucei brucei	Trypanosoma brucei brucei	IC50	>	50000.0	nM	PMID[462931]

☑ 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 NPC248454 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	413
0.1-0.2	4624
0.2-0.3	20941
0.3-0.4	9873
0.4-0.5	2943
0.5-0.6	2038
0.6-0.7	1345
0.7-0.8	409
0.8-0.85	83
0.85-0.9	20
0.9-0.95	6
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9753	High Similarity	NPC163055
0.9313	High Similarity	NPC49954
0.9313	High Similarity	NPC474561
0.9245	High Similarity	NPC282231
0.9182	High Similarity	NPC279918
0.9136	High Similarity	NPC63751
0.9068	High Similarity	NPC194640
0.8957	High Similarity	NPC54988
0.8957	High Similarity	NPC160105
0.8868	High Similarity	NPC469765
0.8868	High Similarity	NPC259644
0.8868	High Similarity	NPC469786
0.8868	High Similarity	NPC73952
0.8868	High Similarity	NPC469760
0.8868	High Similarity	NPC25008
0.8868	High Similarity	NPC469763
0.8812	High Similarity	NPC70922
0.8812	High Similarity	NPC80597
0.8812	High Similarity	NPC75540
0.8812	High Similarity	NPC212376
0.8812	High Similarity	NPC211572
0.881	High Similarity	NPC59269
0.8743	High Similarity	NPC314603
0.8704	High Similarity	NPC469762
0.8688	High Similarity	NPC216713
0.8642	High Similarity	NPC469785
0.8642	High Similarity	NPC285469
0.8616	High Similarity	NPC471957
0.8608	High Similarity	NPC314372
0.8606	High Similarity	NPC311276
0.8481	Intermediate Similarity	NPC190296
0.8457	Intermediate Similarity	NPC470823
0.8452	Intermediate Similarity	NPC201700
0.8439	Intermediate Similarity	NPC233936
0.8436	Intermediate Similarity	NPC294693
0.8434	Intermediate Similarity	NPC16667
0.8424	Intermediate Similarity	NPC230869
0.8421	Intermediate Similarity	NPC267885
0.8405	Intermediate Similarity	NPC200214
0.8395	Intermediate Similarity	NPC24678
0.8395	Intermediate Similarity	NPC105818
0.8383	Intermediate Similarity	NPC40779
0.8363	Intermediate Similarity	NPC149155
0.8363	Intermediate Similarity	NPC110500
0.8363	Intermediate Similarity	NPC203468
0.8354	Intermediate Similarity	NPC207726
0.8343	Intermediate Similarity	NPC78020
0.8343	Intermediate Similarity	NPC165495
0.8324	Intermediate Similarity	NPC248041
0.8324	Intermediate Similarity	NPC126709
0.8295	Intermediate Similarity	NPC15102
0.8263	Intermediate Similarity	NPC131718
0.8261	Intermediate Similarity	NPC159856
0.8249	Intermediate Similarity	NPC235684
0.8242	Intermediate Similarity	NPC272483
0.8239	Intermediate Similarity	NPC469768
0.8239	Intermediate Similarity	NPC469767
0.8239	Intermediate Similarity	NPC469761
0.8239	Intermediate Similarity	NPC469783
0.8239	Intermediate Similarity	NPC469779
0.8239	Intermediate Similarity	NPC469784
0.8239	Intermediate Similarity	NPC469780
0.8222	Intermediate Similarity	NPC473342
0.8222	Intermediate Similarity	NPC477167
0.8218	Intermediate Similarity	NPC283219
0.8218	Intermediate Similarity	NPC213468
0.8204	Intermediate Similarity	NPC67056
0.8202	Intermediate Similarity	NPC317030
0.8187	Intermediate Similarity	NPC194411
0.8187	Intermediate Similarity	NPC280548
0.8187	Intermediate Similarity	NPC469766
0.8176	Intermediate Similarity	NPC73767
0.8165	Intermediate Similarity	NPC84911
0.8161	Intermediate Similarity	NPC145885
0.8161	Intermediate Similarity	NPC14113
0.8161	Intermediate Similarity	NPC68354
0.8161	Intermediate Similarity	NPC151939
0.8161	Intermediate Similarity	NPC84827
0.8156	Intermediate Similarity	NPC321708
0.8156	Intermediate Similarity	NPC213629
0.8146	Intermediate Similarity	NPC474707
0.814	Intermediate Similarity	NPC470498
0.8136	Intermediate Similarity	NPC228835
0.8115	Intermediate Similarity	NPC31385
0.8115	Intermediate Similarity	NPC75726
0.8115	Intermediate Similarity	NPC110602
0.811	Intermediate Similarity	NPC37548
0.8101	Intermediate Similarity	NPC96102
0.8101	Intermediate Similarity	NPC17059
0.8101	Intermediate Similarity	NPC29886
0.8101	Intermediate Similarity	NPC261195
0.8101	Intermediate Similarity	NPC204565
0.8098	Intermediate Similarity	NPC470499
0.8095	Intermediate Similarity	NPC135141
0.8095	Intermediate Similarity	NPC92796
0.8068	Intermediate Similarity	NPC300688
0.8063	Intermediate Similarity	NPC110126
0.8059	Intermediate Similarity	NPC102423
0.8056	Intermediate Similarity	NPC65215
0.8056	Intermediate Similarity	NPC173028
0.805	Intermediate Similarity	NPC105127
0.8046	Intermediate Similarity	NPC37423
0.8046	Intermediate Similarity	NPC275305
0.8045	Intermediate Similarity	NPC94752
0.8042	Intermediate Similarity	NPC323927
0.8036	Intermediate Similarity	NPC129721
0.8012	Intermediate Similarity	NPC470508
0.8011	Intermediate Similarity	NPC55772
0.8011	Intermediate Similarity	NPC95783
0.8011	Intermediate Similarity	NPC11126
0.7989	Intermediate Similarity	NPC314002
0.7989	Intermediate Similarity	NPC188387
0.7989	Intermediate Similarity	NPC163421
0.7989	Intermediate Similarity	NPC313791
0.7988	Intermediate Similarity	NPC143872
0.7976	Intermediate Similarity	NPC141353
0.7975	Intermediate Similarity	NPC242556
0.7955	Intermediate Similarity	NPC111275
0.7952	Intermediate Similarity	NPC53947
0.7952	Intermediate Similarity	NPC148592
0.7944	Intermediate Similarity	NPC171171
0.7933	Intermediate Similarity	NPC204717
0.7923	Intermediate Similarity	NPC99666
0.7923	Intermediate Similarity	NPC477166
0.7923	Intermediate Similarity	NPC304187
0.7921	Intermediate Similarity	NPC71037
0.7917	Intermediate Similarity	NPC38736
0.7917	Intermediate Similarity	NPC470507
0.7914	Intermediate Similarity	NPC470497
0.791	Intermediate Similarity	NPC176199
0.791	Intermediate Similarity	NPC215795
0.7901	Intermediate Similarity	NPC279081
0.7892	Intermediate Similarity	NPC187951
0.7886	Intermediate Similarity	NPC34508
0.7882	Intermediate Similarity	NPC206819
0.7882	Intermediate Similarity	NPC318065
0.788	Intermediate Similarity	NPC474177
0.7879	Intermediate Similarity	NPC288838
0.7877	Intermediate Similarity	NPC220765
0.7849	Intermediate Similarity	NPC227582
0.7848	Intermediate Similarity	NPC82295
0.7838	Intermediate Similarity	NPC133366
0.7807	Intermediate Similarity	NPC171317
0.7807	Intermediate Similarity	NPC473640
0.7802	Intermediate Similarity	NPC46580
0.7791	Intermediate Similarity	NPC230002
0.779	Intermediate Similarity	NPC280290
0.7785	Intermediate Similarity	NPC22079
0.7784	Intermediate Similarity	NPC321911
0.7784	Intermediate Similarity	NPC124005
0.7784	Intermediate Similarity	NPC472123
0.7778	Intermediate Similarity	NPC48938
0.7778	Intermediate Similarity	NPC469358
0.7766	Intermediate Similarity	NPC100321
0.7766	Intermediate Similarity	NPC293917
0.7759	Intermediate Similarity	NPC49217
0.7754	Intermediate Similarity	NPC229332
0.7754	Intermediate Similarity	NPC262898
0.7747	Intermediate Similarity	NPC62749
0.7747	Intermediate Similarity	NPC315555
0.774	Intermediate Similarity	NPC472586
0.7737	Intermediate Similarity	NPC476874
0.7737	Intermediate Similarity	NPC193761
0.7725	Intermediate Similarity	NPC179787
0.7725	Intermediate Similarity	NPC23420
0.7725	Intermediate Similarity	NPC303820
0.7725	Intermediate Similarity	NPC469811
0.7725	Intermediate Similarity	NPC205254
0.7725	Intermediate Similarity	NPC106771
0.7725	Intermediate Similarity	NPC201380
0.7725	Intermediate Similarity	NPC252338
0.7719	Intermediate Similarity	NPC286427
0.7714	Intermediate Similarity	NPC317430
0.7711	Intermediate Similarity	NPC285731
0.7709	Intermediate Similarity	NPC219336
0.7709	Intermediate Similarity	NPC270009
0.7709	Intermediate Similarity	NPC472443
0.7706	Intermediate Similarity	NPC471458
0.7701	Intermediate Similarity	NPC11445
0.7701	Intermediate Similarity	NPC179701
0.7697	Intermediate Similarity	NPC288785
0.7688	Intermediate Similarity	NPC307963
0.7684	Intermediate Similarity	NPC475506
0.7684	Intermediate Similarity	NPC475935
0.7684	Intermediate Similarity	NPC94211
0.7684	Intermediate Similarity	NPC52909
0.7674	Intermediate Similarity	NPC41257
0.7674	Intermediate Similarity	NPC56765
0.7667	Intermediate Similarity	NPC91179
0.7665	Intermediate Similarity	NPC63545
0.766	Intermediate Similarity	NPC77555
0.7654	Intermediate Similarity	NPC183662
0.7654	Intermediate Similarity	NPC15573
0.7654	Intermediate Similarity	NPC184964
0.7654	Intermediate Similarity	NPC217372
0.7647	Intermediate Similarity	NPC195239
0.7647	Intermediate Similarity	NPC157828
0.7647	Intermediate Similarity	NPC325903
0.7644	Intermediate Similarity	NPC155143
0.764	Intermediate Similarity	NPC329688

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 NPC248454 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	201
0.1-0.2	616
0.2-0.3	1040
0.3-0.4	1565
0.4-0.5	2623
0.5-0.6	2147
0.6-0.7	816
0.7-0.8	122
0.8-0.85	17
0.85-0.9	2
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9006	High Similarity	NPD8110	Clinical (unspecified phase)
0.8848	High Similarity	NPD4184	Clinical (unspecified phase)
0.8596	High Similarity	NPD6595	Phase 3
0.8421	Intermediate Similarity	NPD749	Clinical (unspecified phase)
0.8415	Intermediate Similarity	NPD8073	Approved
0.837	Intermediate Similarity	NPD8072	Approved
0.8363	Intermediate Similarity	NPD482	Approved
0.8305	Intermediate Similarity	NPD8431	Approved
0.8295	Intermediate Similarity	NPD6610	Clinical (unspecified phase)
0.8286	Intermediate Similarity	NPD2095	Phase 2
0.8286	Intermediate Similarity	NPD2094	Phase 2
0.8286	Intermediate Similarity	NPD2092	Phase 2
0.8239	Intermediate Similarity	NPD2091	Phase 2
0.8239	Intermediate Similarity	NPD2096	Phase 2
0.8226	Intermediate Similarity	NPD8272	Phase 2
0.8221	Intermediate Similarity	NPD3100	Discontinued
0.8218	Intermediate Similarity	NPD4079	Approved
0.8218	Intermediate Similarity	NPD4076	Approved
0.8182	Intermediate Similarity	NPD5728	Clinical (unspecified phase)
0.8176	Intermediate Similarity	NPD786	Approved
0.8161	Intermediate Similarity	NPD3505	Approved
0.8161	Intermediate Similarity	NPD6203	Clinical (unspecified phase)
0.8161	Intermediate Similarity	NPD3506	Approved
0.8161	Intermediate Similarity	NPD2144	Approved
0.815	Intermediate Similarity	NPD5065	Approved
0.811	Intermediate Similarity	NPD4374	Clinical (unspecified phase)
0.8101	Intermediate Similarity	NPD198	Clinical (unspecified phase)
0.8092	Intermediate Similarity	NPD750	Phase 2
0.8075	Intermediate Similarity	NPD1722	Approved
0.8047	Intermediate Similarity	NPD1404	Approved
0.8047	Intermediate Similarity	NPD1403	Approved
0.8035	Intermediate Similarity	NPD3610	Approved
0.8035	Intermediate Similarity	NPD3609	Approved
0.8023	Intermediate Similarity	NPD3038	Discontinued
0.8023	Intermediate Similarity	NPD2640	Approved
0.8023	Intermediate Similarity	NPD2641	Approved
0.8023	Intermediate Similarity	NPD5069	Clinical (unspecified phase)
0.7978	Intermediate Similarity	NPD5575	Clinical (unspecified phase)
0.7965	Intermediate Similarity	NPD2642	Approved
0.7965	Intermediate Similarity	NPD2639	Approved
0.7919	Intermediate Similarity	NPD2185	Clinical (unspecified phase)
0.7901	Intermediate Similarity	NPD5590	Clinical (unspecified phase)
0.7877	Intermediate Similarity	NPD5106	Approved
0.7877	Intermediate Similarity	NPD5105	Approved
0.7874	Intermediate Similarity	NPD1326	Approved
0.7874	Intermediate Similarity	NPD1325	Approved
0.7849	Intermediate Similarity	NPD7948	Phase 1
0.7844	Intermediate Similarity	NPD2172	Phase 1
0.7844	Intermediate Similarity	NPD4463	Approved
0.7844	Intermediate Similarity	NPD4462	Approved
0.7841	Intermediate Similarity	NPD4128	Approved
0.7772	Intermediate Similarity	NPD2125	Clinical (unspecified phase)
0.7766	Intermediate Similarity	NPD7621	Clinical (unspecified phase)
0.7765	Intermediate Similarity	NPD8464	Clinical (unspecified phase)
0.7732	Intermediate Similarity	NPD7825	Clinical (unspecified phase)
0.7725	Intermediate Similarity	NPD1661	Suspended
0.7714	Intermediate Similarity	NPD4640	Approved
0.7714	Intermediate Similarity	NPD4639	Approved
0.7714	Intermediate Similarity	NPD4638	Approved
0.7709	Intermediate Similarity	NPD8386	Phase 2
0.7705	Intermediate Similarity	NPD3961	Discontinued
0.7697	Intermediate Similarity	NPD6375	Clinical (unspecified phase)
0.7697	Intermediate Similarity	NPD4075	Phase 2
0.7688	Intermediate Similarity	NPD1038	Approved
0.7688	Intermediate Similarity	NPD1304	Clinical (unspecified phase)
0.7656	Intermediate Similarity	NPD5901	Discontinued
0.7647	Intermediate Similarity	NPD2837	Discontinued
0.7627	Intermediate Similarity	NPD5934	Clinical (unspecified phase)
0.7619	Intermediate Similarity	NPD4703	Approved
0.7619	Intermediate Similarity	NPD4702	Approved
0.7617	Intermediate Similarity	NPD7957	Phase 1
0.7617	Intermediate Similarity	NPD7958	Clinical (unspecified phase)
0.7588	Intermediate Similarity	NPD5818	Discontinued
0.7577	Intermediate Similarity	NPD8493	Clinical (unspecified phase)
0.7556	Intermediate Similarity	NPD4181	Approved
0.7543	Intermediate Similarity	NPD3323	Discontinued
0.7538	Intermediate Similarity	NPD7947	Clinical (unspecified phase)
0.7526	Intermediate Similarity	NPD4862	Clinical (unspecified phase)
0.7514	Intermediate Similarity	NPD3486	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD2719	Clinical (unspecified phase)
0.75	Intermediate Similarity	NPD2720	Phase 1
0.75	Intermediate Similarity	NPD802	Phase 2
0.7486	Intermediate Similarity	NPD5315	Discontinued
0.7474	Intermediate Similarity	NPD5426	Phase 3
0.747	Intermediate Similarity	NPD3943	Clinical (unspecified phase)
0.7463	Intermediate Similarity	NPD7711	Discontinued
0.7462	Intermediate Similarity	NPD7998	Clinical (unspecified phase)
0.7448	Intermediate Similarity	NPD484	Approved
0.7447	Intermediate Similarity	NPD3404	Approved
0.7425	Intermediate Similarity	NPD1592	Phase 3
0.7424	Intermediate Similarity	NPD7470	Discontinued
0.7424	Intermediate Similarity	NPD8013	Clinical (unspecified phase)
0.7401	Intermediate Similarity	NPD5744	Clinical (unspecified phase)
0.74	Intermediate Similarity	NPD7970	Approved
0.74	Intermediate Similarity	NPD7971	Clinical (unspecified phase)
0.7387	Intermediate Similarity	NPD8458	Clinical (unspecified phase)
0.7387	Intermediate Similarity	NPD7594	Clinical (unspecified phase)
0.7386	Intermediate Similarity	NPD8026	Phase 1
0.7386	Intermediate Similarity	NPD2385	Clinical (unspecified phase)
0.7371	Intermediate Similarity	NPD3015	Discontinued
0.7368	Intermediate Similarity	NPD7619	Phase 3
0.7368	Intermediate Similarity	NPD7618	Phase 3
0.7366	Intermediate Similarity	NPD6217	Discontinued
0.735	Intermediate Similarity	NPD8488	Clinical (unspecified phase)
0.7345	Intermediate Similarity	NPD5138	Approved
0.7345	Intermediate Similarity	NPD5140	Approved
0.7337	Intermediate Similarity	NPD5254	Discontinued
0.7318	Intermediate Similarity	NPD5021	Discontinued
0.7318	Intermediate Similarity	NPD4779	Clinical (unspecified phase)
0.7313	Intermediate Similarity	NPD8112	Clinical (unspecified phase)
0.7308	Intermediate Similarity	NPD5100	Phase 3
0.7288	Intermediate Similarity	NPD972	Clinical (unspecified phase)
0.7288	Intermediate Similarity	NPD1853	Clinical (unspecified phase)
0.7286	Intermediate Similarity	NPD7809	Clinical (unspecified phase)
0.7283	Intermediate Similarity	NPD6277	Clinical (unspecified phase)
0.7278	Intermediate Similarity	NPD4637	Clinical (unspecified phase)
0.7277	Intermediate Similarity	NPD7944	Discontinued
0.7273	Intermediate Similarity	NPD706	Phase 1
0.7258	Intermediate Similarity	NPD3607	Clinical (unspecified phase)
0.7251	Intermediate Similarity	NPD1528	Clinical (unspecified phase)
0.7249	Intermediate Similarity	NPD5117	Phase 2
0.7249	Intermediate Similarity	NPD4499	Approved
0.7241	Intermediate Similarity	NPD8406	Clinical (unspecified phase)
0.7241	Intermediate Similarity	NPD2012	Clinical (unspecified phase)
0.724	Intermediate Similarity	NPD7818	Clinical (unspecified phase)
0.7239	Intermediate Similarity	NPD3476	Approved
0.7239	Intermediate Similarity	NPD3475	Approved
0.7234	Intermediate Similarity	NPD6141	Clinical (unspecified phase)
0.7222	Intermediate Similarity	NPD6838	Clinical (unspecified phase)
0.7222	Intermediate Similarity	NPD2844	Phase 3
0.7222	Intermediate Similarity	NPD4865	Approved
0.7216	Intermediate Similarity	NPD1315	Clinical (unspecified phase)
0.7213	Intermediate Similarity	NPD6044	Discontinued
0.7211	Intermediate Similarity	NPD6180	Clinical (unspecified phase)
0.7209	Intermediate Similarity	NPD4547	Phase 3
0.7206	Intermediate Similarity	NPD8405	Clinical (unspecified phase)
0.72	Intermediate Similarity	NPD3843	Clinical (unspecified phase)
0.7192	Intermediate Similarity	NPD5612	Discontinued
0.7181	Intermediate Similarity	NPD4426	Clinical (unspecified phase)
0.7178	Intermediate Similarity	NPD3654	Approved
0.7176	Intermediate Similarity	NPD3717	Discontinued
0.7176	Intermediate Similarity	NPD2006	Phase 2
0.7175	Intermediate Similarity	NPD5255	Approved
0.7168	Intermediate Similarity	NPD2430	Phase 2
0.716	Intermediate Similarity	NPD2119	Approved
0.716	Intermediate Similarity	NPD2118	Approved
0.716	Intermediate Similarity	NPD991	Phase 2
0.716	Intermediate Similarity	NPD992	Clinical (unspecified phase)
0.7158	Intermediate Similarity	NPD2928	Phase 2
0.7151	Intermediate Similarity	NPD6148	Clinical (unspecified phase)
0.7143	Intermediate Similarity	NPD3117	Approved
0.7143	Intermediate Similarity	NPD2310	Clinical (unspecified phase)
0.7143	Intermediate Similarity	NPD3116	Approved
0.7135	Intermediate Similarity	NPD3401	Clinical (unspecified phase)
0.7129	Intermediate Similarity	NPD8093	Discontinued
0.7127	Intermediate Similarity	NPD5862	Discovery
0.712	Intermediate Similarity	NPD4949	Discontinued
0.7113	Intermediate Similarity	NPD6664	Approved
0.7108	Intermediate Similarity	NPD3385	Approved
0.7108	Intermediate Similarity	NPD6803	Clinical (unspecified phase)
0.7104	Intermediate Similarity	NPD4112	Clinical (unspecified phase)
0.7099	Intermediate Similarity	NPD9583	Approved
0.7092	Intermediate Similarity	NPD5043	Discontinued
0.7086	Intermediate Similarity	NPD6476	Clinical (unspecified phase)
0.7086	Intermediate Similarity	NPD6158	Phase 2
0.7083	Intermediate Similarity	NPD4615	Phase 2
0.7081	Intermediate Similarity	NPD1272	Clinical (unspecified phase)
0.7079	Intermediate Similarity	NPD5067	Phase 2
0.7079	Intermediate Similarity	NPD704	Clinical (unspecified phase)
0.7079	Intermediate Similarity	NPD5066	Phase 2
0.7077	Intermediate Similarity	NPD3469	Phase 3
0.7076	Intermediate Similarity	NPD2007	Clinical (unspecified phase)
0.7074	Intermediate Similarity	NPD6178	Phase 3
0.7071	Intermediate Similarity	NPD2121	Clinical (unspecified phase)
0.7065	Intermediate Similarity	NPD6492	Phase 2
0.7062	Intermediate Similarity	NPD2580	Discontinued
0.7062	Intermediate Similarity	NPD276	Clinical (unspecified phase)
0.7059	Intermediate Similarity	NPD3178	Discontinued
0.7056	Intermediate Similarity	NPD4511	Phase 1
0.7056	Intermediate Similarity	NPD7903	Clinical (unspecified phase)
0.7052	Intermediate Similarity	NPD1683	Approved
0.705	Intermediate Similarity	NPD1392	Approved
0.7047	Intermediate Similarity	NPD2717	Phase 2
0.7044	Intermediate Similarity	NPD3330	Phase 1
0.7043	Intermediate Similarity	NPD8036	Clinical (unspecified phase)
0.7043	Intermediate Similarity	NPD8037	Clinical (unspecified phase)
0.7041	Intermediate Similarity	NPD5828	Phase 2
0.7041	Intermediate Similarity	NPD3825	Phase 3
0.7041	Intermediate Similarity	NPD2896	Discontinued
0.7035	Intermediate Similarity	NPD3813	Approved
0.7035	Intermediate Similarity	NPD751	Clinical (unspecified phase)
0.7035	Intermediate Similarity	NPD4509	Discontinued
0.7033	Intermediate Similarity	NPD6173	Approved
0.7031	Intermediate Similarity	NPD1235	Phase 3
0.7031	Intermediate Similarity	NPD6630	Clinical (unspecified phase)
0.7027	Intermediate Similarity	NPD2381	Approved
0.7027	Intermediate Similarity	NPD3348	Phase 2
0.7027	Intermediate Similarity	NPD2382	Approved
0.7027	Intermediate Similarity	NPD2380	Approved
0.7024	Intermediate Similarity	NPD792	Discontinued

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